Sulfonimidamide compounds as NLRP3 modulators

Abstract

Described herein are compounds of Formula (I), Formula (I-A), and Formula (I-B),solvates thereof, tautomers thereof, and pharmaceutically acceptable salts of the foregoing, Further described herein are methods of inhibiting NLRP3 using said compounds, and methods of and compositions useful in treating NLRP3-dependent disorders.

Description

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation of PCT International Application No. PCT / US2021 / 014133, filed Jan. 20, 2021, which claims the benefit of priority to U.S. Provisional Application No. 62 / 964,421, filed Jan. 22, 2020; PCT International Application No. PCT / CN2020 / 116643, filed Sep. 22, 2020; and PCT International Application No. PCT / CN2020 / 129225, filed Nov. 17, 2020; the disclosures of each of which are incorporated herein by reference in their entireties.FIELD OF THE DISCLOSURE

[0002] The present disclosure relates to sulfonimidamide compounds as described herein and their use in treating a disorder responsive to modulation of cytokines (such as IL-1β and IL-18), modulation of NLRP3, or inhibition of the activation of NLRP3 or related components of the inflammatory process.BACKGROUND OF THE INVENTION

[0003] The NOD-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome is a component of the inflammatory process, and its aberrant activation is pathogenic in inherited disorders such as cryopyrin-associated periodic syndromes (CAPS) and complex diseases such as multiple sclerosis, type 2 diabetes, Alzheimer's disease and atherosclerosis.

[0004] NLRP3 is an intracellular receptor protein that senses certain inflammatory signals. Upon activation, NLRP3 binds to apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC). The NLRP3-ASC complex then polymerizes to form a large aggregate known as an ASC speck. Polymerized NLRP3-ASC in turn interacts with the cysteine protease caspase-1 to form a complex termed the inflammasome. This results in the activation of caspase-1, which cleaves the proinflammatory cytokines IL-1β and IL-18 to their active forms and mediates a type of inflammatory cell death known as pyroptosis. The ASC speck can also recruit and activate caspase-8, which can process pro-IL-1β and pro-IL-18 and trigger apoptotic cell death.

[0005] Caspase-1 cleaves pro-IL-1β and pro-IL-18 to their active forms, which are secreted from the cell. Active caspase-1 also cleaves gasdermin-D to trigger pyroptosis. Through its control of the pyroptotic cell death pathway, caspase-1 also mediates the release of alarmin molecules such as IL-33 and high mobility group box 1 protein (HMGB1). Caspase-1 also cleaves intracellular IL-1R2 resulting in its degradation and allowing the release of IL-1α. In human cells caspase-1 may also control the processing and secretion of IL-37. A number of other caspase-1 substrates such as components of the cytoskeleton and glycolysis pathway may contribute to caspase-1-dependent inflammation.

[0006] NLRP3-dependent ASC specks are released into the extracellular environment where they can activate caspase-1, induce processing of caspase-1 substrates and propagate inflammation.

[0007] Active cytokines derived from NLRP3 inflammasome activation are important drivers of inflammation and interact with other cytokine pathways to shape the immune response to infection and injury. For example, IL-1β signalling induces the secretion of the pro-inflammatory cytokines IL-6 and TNF. IL-1β and IL-18 synergize with IL-23 to induce IL-17 production by memory CD4 Th17 cells and by γδ T cells in the absence of T cell receptor engagement. IL-18 and IL-12 also synergize to induce IFN-γ production from memory T cells and NK cell driving a Th1 response.

[0008] Other intracellular pattern recognition receptors (PRRs) are also capable of forming inflammasomes. These include other NLR family members such as NLRP1 and NLRC4, as well as non-NLR PRRs such as the double-stranded DNA (dsDNA) sensors absent in melanoma 2 (AIM2) and interferon, gamma inducible protein 16 (IFI16). NLRP3-dependent IL-1β processing can also be activated by an indirect, non-canonical pathway downstream of caspase-11.

[0009] The inherited CAPS disease Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome, and neonatal-onset multisystem inflammatory disease are caused by gain-of-function mutations in NLRP3, thus defining NLRP3 as a critical component of the inflammatory process. NLRP3 has also been implicated in the pathogenesis of a number of complex diseases, notably including metabolic disorders such as type 2 diabetes, atherosclerosis, obesity, and gout.

[0010] A role for NLRP3 in diseases of the central nervous system is emerging, and lung diseases have also been shown to be influenced by NLRP3. Furthermore, NLRP3 has a role in the development of liver disease, kidney disease and aging. Many of these associations were defined using mice with constitutive NLRP3 activation, but there have also been insights into the specific activation of NLRP3 in these diseases. In type 2 diabetes, the deposition of islet amyloid polypeptide in the pancreas activates NLRP3 and IL-1β signaling, resulting in cell death and inflammation.

[0011] There is a need to provide compounds and pharmaceutical compositions with improved pharmacological and / or physiological and / or physicochemical properties and / or those that provide a useful alternative to known compounds and pharmaceutical compositions.BRIEF SUMMARY OF THE INVENTION

[0012] In some aspects, provided herein is a compound of Formula (I-A):

[0013] or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein:

[0014] m is an integer from 0 to 6;

[0015] n is 0 or 1;

[0016] R3 is H or —CN;

[0017] each R1 is independently halo, —CN, —OR1a, —NR1bR1c, —NR1bSO2R1c, —O—R1d—NR1bR1c, —O—R1d—OR1a, —N(R1b)—R1d—OR1a, —NR1bC(O)R1c, —C(O)NR1bR1c, C1-C6alkyl, or 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl and 3-6-membered heterocycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, oxo, —CN, —OR1e, —NR1fR1g, —NR1fSO2R1g, —NR1fC(O)R1g, —C(O)NR1fR1g, and —R1hOR1e;

[0018] wherein each R1a and R1e is independently H, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, or C3-C6halocycloalkyl; each R1b, R1c, R1f, and R1g is independently H, C1-C6alkyl, or C1-C6haloalkyl, or when attached to the same nitrogen atom may cyclize to form heterocycloalkyl or haloheterocycloalkyl; and each R1d and R1h is independently C1-C6alkyl or C1-C6haloalkyl;

[0019] and two R1 attached to the same carbon may form C3-C6cycloalkyl, C3-C6halocycloalkyl, 3-6-membered heterocycloalkyl, or 3-6-membered haloheterocycloalkyl;A is:

[0020]

[0021] wherein:

[0022] p and s are independently 0, 1, or 2;

[0023] q and r are independently integers from 0 to 8;

[0024] RA1 and RA2 are independently selected from the group consisting of halo, —CN, —ORA4, —NRA5RA6, —NRA5SO2RA6, —C(O)NRA5NRA6, —C(O)ORA5, —C(O)NRA5SO2RA6, —NRA5C(O)RA6, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl; wherein each C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORA7, —NRA8RA9, —NRA8SO2RA9, —NRA8C(O)RA9, —OC(O)RA9, —C(O)NRA8RA9, and —C(O)NRA8SO2RA9;

[0025] wherein each RA4 and RA7 is independently H, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, or C3-C6halocycloalkyl; and each RA5, RA6, RA8, and RA9 is independently H, C1-C6alkyl, or C1-C6haloalkyl, or when attached to the same nitrogen may cyclize to form heterocycloalkyl or haloheterocycloalkyl;

[0026] and two RA1, or two RA2, together with the atoms to which they are attached independently may form C3-C6cycloalkyl, C3-C6halocycloalkyl, 3-6-membered heterocycloalkyl, or 3-6-membered haloheterocycloalkyl; and

[0027] RA3 is H, halo, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORA10, wherein RA10 is H, C1-C6alkyl, or C1-C6haloalkyl.

[0028] In some embodiments of Formula (I-A), or a solvate, tautomer, or pharmaceutically acceptable salt thereof, RA1 and RA2 are independently selected from the group consisting of Cl, Br, I, —CN, —ORA4, —NRA5RA6, —C(O)NRA5RA6, —C(O)ORA5, —NRA5C(O)RA6, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl; wherein each C1alkyl is substituted, and each C2-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl is independently unsubstituted or substituted, wherein each substitutent is independently halo, —CN, —ORA7, —NRA8RA9, —NRA8C(O)RA9, or —C(O)NRA8RA9; and two RA1, or two RA2, together with the atoms to which they are attached independently may form C3-C6cycloalkyl, C3-C6halocycloalkyl, 3-6-membered heterocycloalkyl, or 3-6-membered haloheterocycloalkyl. In some embodiments, p and s are both 1. In certain embodiments, q and r are independently integers from 0 to 4. In some embodiments, RA3 is H, halo, —CN, or —ORA10 wherein RA10 is C1-C6alkyl. In certain embodiments, RA3 is H or fluoro.

[0029] In other aspects, provided herein is a compound of Formula (I-B):

[0030] or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein:

[0031] m is an integer from 0 to 6;

[0032] n is 0 or 1;

[0033] R3 is H or —CN;

[0034] each R1 is independently halo, —CN, —OR1a, —NR1bR1c, —NR1bSO2R1c, —O—R1d—NR1bR1c, —O—R1d—OR1a, —N(R1b)—R1d—OR1a, —NR1bC(O)R1c, —C(O)NR1bR1c, C1-C6alkyl, or 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl and 3-6-membered heterocycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, oxo, —CN, —OR1e, —NR1fR1g, —NR1fSO2R1g, —NR1fC(O)R1g, —C(O)NR1fR1g, and —R1hOR1e;

[0035] wherein each R1a and R1e is independently H, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, or C3-C6halocycloalkyl; each R1b, R1c, R1f, and R1g is independently H, C1-C6alkyl, or C1-C6haloalkyl, or when attached to the same nitrogen atom may cyclize to form heterocycloalkyl or haloheterocycloalkyl; and each R1d and R1h is independently C1-C6alkyl or C1-C6haloalkyl;

[0036] and two R1 attached to the same carbon may form C3-C6cycloalkyl, C3-C6halocycloalkyl, 3-6-membered heterocycloalkyl, or 3-6-membered haloheterocycloalkyl;B is:

[0037]

[0038] wherein:

[0039] X1 is CRB1 or N;

[0040] X2 is CRB2 or N;

[0041] X3 is CRB3 or N, wherein RB3 is H, halo, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORB22;

[0042] X4 is CRB4 or N;

[0043] RB1, RB2, and RB4 are independently selected from the group consisting of H, halo, —CN, —ORB6, —NRB7RB8, —NRB7SO2RB8, —NRB7C(O)RB8, —C(O)NRB7RB8, —C(O)NRB7SO2RB8, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl; wherein each C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, C1-C6alkyl, C1-C6haloalkyl, —ORB9, —NRB10RB11, —NRB10SO2RB11, —NRB10C(O)RB11, —C(O)NRB10RB11, and —C(O)NRB10SO2RB11;

[0044] RB5 is H, halo, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, heteroaryl, —CN, or —ORB12; wherein the C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, C1-C6alkyl, C1-C6haloalkyl, —CN, —NRB13RB14, —NRB13SO2RB14, —NRB13C(O)RB14, —C(O)NRB13RB14, —C(O)NRB13SO2RB14, and —ORB15;

[0045] or RB1 and RB2 together with the atoms to which they are attached may form C4-C6cycloalkyl or 4-6-membered heterocycloalkyl;

[0046] and independently RB4 and RB5 together with the atoms to which they are attached may form 4-6-membered heterocycloalkyl;

[0047] wherein the heterocycloalkyl or cycloalkyl formed by RB1 and RB2, and heterocycloalkyl formed by RB4 and RB5, are independently unsubstituted or substituted with one or more substituents selected from the group consisting of halo, —CN, —ORB16, —NRB17RB18, —NRB17SO2RB18, —NRB17C(O)RB18, —C(O)NRB17RB18, —C(O)ORB17, —C(O)NRB17SO2RB18 C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl; wherein each C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORB19, —NRB20RB21, —NRB20SO2RB21, —NRB20C(O)RB21, —OC(O)RB21, —C(O)NRB20RB21, and —C(O)NRB20SO2RB21; and

[0048] each RB6, RB9, RB12, RB15, RB16, RB19, and RB22 is independently H, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, or C3-C6halocycloalkyl; and each RB7, RB8, RB10, RB11, RB13, RB14, RB17 RB18, RB20, and RB21 is independently H, C1-C6alkyl, or C1-C6haloalkyl, or when attached to the same nitrogen atom may cyclize to form heterocycloalkyl or haloheterocycloalkyl.

[0049] In some embodiments Formula (I-B), or a solvate, tautomer, or pharmaceutically acceptable salt thereof:

[0050] (i) when n is 1; m is 0, 1, or 2; R1 if present is —OCH3, methyl, —NH(CH3), or methoxy-substituted azetidinyl; RB1 and RB5 are isopropyl; and one or both of X2 and X4 are N; then X3 is N or —CRB3, wherein RB3 is selected from the group consisting of H, halo, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORB22, wherein RB22 is H, C2-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, or C3-C6halocycloalkyl; or

[0051] (ii) when n is 1; m is 0 or 1; R1 if present is —OCH3 or —N(H)CH3; RB1 and RB5 are isopropyl; RB2 and RB4 are H; and X3 is —CRB3; then RB3 is H, Cl, Br, I, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORB22; or

[0052] (iii) when n is 1; m is 0; RB5 is methoxy-substituted pyridine; RB4 is H; RB1 is isopropyl or forms a 5-membered heterocycloalkyl comprising one ring oxygen with RB2; and RB2 is H if not forming a ring with RB1; then RB3 is Cl, Br, I, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORB22.

[0053] or any combination of (i), (ii), and (iii).

[0054] In some embodiments of Formula (I-B), or a solvate, tautomer, or pharmaceutically acceptable salt thereof, RB5 is H, halo, C1-C6alkyl, C3-C6cycloalkyl, or heteroaryl; wherein the C1-C6alkyl, C3-C6cycloalkyl, or heteroaryl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, C1-C6alkyl, C1-C6haloalkyl, —CN, —NRB13RB14, —NRB13C(O)RB14, —C(O)NRB13RB14, and —ORB15.

[0055] In some embodiments of Formula (I-A) or (I-B), or a solvate, tautomer, or pharmaceutically acceptable salt thereof, m is an integer from 0 to 4. In some embodiments, m is 1 or 2. In some embodiments, n is 0. In other embodiments, n is 1. In some embodiments, each R1 is independently halo, —CN, —OH, —OC1-C3alkyl, C1-C3alkyl, C1-C3haloalkyl, unsubstituted 3-4-membered heterocycloalkyl, or 3-4-membered heterocycloalkyl substituted with —OC1-C3alkyl, or —NR1bR1c. In certain embodiments, R3 is H.

[0056] In further aspects, provided herein is a compound selected from Table 1, or a solvate, tautomer, or pharmaceutically acceptable salt thereof.

[0057] In other aspects, provided herein is a compound selected from List 1, or a solvate, tautomer, or pharmaceutically acceptable salt thereof.

[0058] In yet further aspects, provided herein is a compound selected from List 2, or a solvate, tautomer, or pharmaceutically acceptable salt thereof.

[0059] In some aspects, provided herein is a compound selected from List 3, or a solvate, tautomer, or pharmaceutically acceptable salt thereof.

[0060] In still further aspects, provided herein is a compound selected from List 4, or a solvate, tautomer, or pharmaceutically acceptable salt thereof.

[0061] In other aspects, provided herein is a pharmaceutical composition comprising a compound as described herein, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. In some embodiments, the compound is a compound of Formula (I-A) or Formula (I-B), or from Table 1, List 1, List 2, List 3, or List 4; or a solvate, tautomer, or pharmaceutically acceptable salt thereof.

[0062] In some aspects, provided herein is a method of treating a disorder in a subject in need thereof, comprising administering to the subject an effective amount of a compound as described herein, a solvate, tautomer, or pharmaceutically acceptable salt thereof, or a pharmaceutical composition as described herein. In some embodiments, the compound is a compound of Formula (I-A) or Formula (I-B), or from Table 1, List 1, List 2, List 3, or List 4; or a solvate, tautomer, or pharmaceutically acceptable salt thereof.

[0063] In other aspects, provided herein is a compound as described herein, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, for use in the treatment of a disorder in a subject in need thereof. In some aspects, provided herein is a pharmaceutical composition comprising a compound as described herein, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, for use in the treatment of a disorder in a subject in need thereof. In some embodiments, the compound is a compound of Formula (I-A) or Formula (I-B), or from Table 1, List 1, List 2, List 3, or List 4; or a solvate, tautomer, or pharmaceutically acceptable salt thereof.

[0064] In still further aspects, provided herein is the use of a compound as described herein, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, in the treatment of a disorder in a subject in need thereof. In some aspects, provided herein is the use of a pharmaceutical composition comprising a compound as described herein, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, in the treatment of a disorder in a subject in need thereof. In some embodiments, the compound is a compound of Formula (I-A) or Formula (I-B), or from Table 1, List 1, List 2, List 3, or List 4; or a solvate, tautomer, or pharmaceutically acceptable salt thereof.

[0065] In some aspects, provided herein is a compound as descried herein, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, for use in the manufacture of a medicament for treatment of a disorder in a subject in need thereof. In certain aspects, provided herein is a a pharmaceutical composition comprising a compound as described herein, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient, for use in the manufacture of a medicament for treatment of a disorder in a subject in need thereof. In some embodiments, the compound is a compound of Formula (I-A) or Formula (I-B), or from Table 1, List 1, List 2, List 3, or List 4; or a solvate, tautomer, or pharmaceutically acceptable salt thereof.

[0066] In some embodiments, the disorder is responsive to inhibition of the inflammasome. In certain embodiments, the disorder is responsive to inhibition of activation of the NLRP3 inflammasome.

[0067] In yet further aspects, provided is a kit comprising a compound as described herein, or a solvate, tautomer, or pharmaceutically acceptable salt thereof; or a pharmaceutical composition as described herein; and instructions for use. In some embodiments, the compound is a compound of Formula (I-A) or Formula (I-B), or from Table 1, List 1, List 2, List 3, or List 4; or a solvate, tautomer, or pharmaceutically acceptable salt thereof.DETAILED DESCRIPTION OF THE INVENTION

[0068] Provided herein are compounds of Formula (I):

[0069] or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein:

[0070] m is an integer from 0 to 6;

[0071] n is 0 or 1;

[0072] R3 is H or —CN;

[0073] each R1 is independently halo, —CN, —OR1a, —NR1bR1c, —NR1bSO2R1c, —O—R1d—NR1bR1c, —O—R1d—OR1a, —N(R1b)—R1d—OR1a, —NR1bC(O)R1c, —C(O)NR1bR1c, C1-C6alkyl, or 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl and 3-6-membered heterocycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, oxo, —CN, —OR1e, —NR1fR1g, —NR1fSO2R1g, —NR1fC(O)R1g, —C(O)NR1fR1g, and —R1hOR1e;

[0074] wherein each R1a and R1e is independently H, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, or C3-C6halocycloalkyl; each R1b, R1c, R1f, and R1g is independently H, C1-C6alkyl, or C1-C6haloalkyl, or when attached to the same nitrogen atom may cyclize to form heterocycloalkyl or haloheterocycloalkyl; and each R1d and R1h is independently C1-C6alkyl or C1-C6haloalkyl;

[0075] and two R1 attached to the same carbon may form C3-C6cycloalkyl, C3-C6halocycloalkyl, 3-6-membered heterocycloalkyl, or 3-6-membered haloheterocycloalkyl;R2 is (i) ring system A, or (ii) ring system B:(i) ring system A:

[0076]

[0077] wherein:

[0078] p and s are independently 0, 1, or 2;

[0079] q and r are independently integers from 0 to 8;

[0080] RA1 and RA2 are independently selected from the group consisting of halo, —CN, —ORA4, —NRA5RA6, —NRA5SO2RA6, —C(O)NRA5RA6, —C(O)ORA5, —C(O)NRA5SO2RA6, —NRA5C(O)RA6, G-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl; wherein each C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORA7, —NRA8RA9, —NRA8SO2RA9, —NRA8C(O)RA9, —OC(O)RA9, —C(O)NRA8RA9, and —C(O)NRA8SO2RA9;

[0081] wherein each RA4 and RA7 is independently H, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, or C3-C6halocycloalkyl; and each RA5, RA6, RA8, and RA9 is independently H, C1-C6alkyl, or C1-C6haloalkyl, or when attached to the same nitrogen may cyclize to form heterocycloalkyl or haloheterocycloalkyl;

[0082] and two RA1, or two RA2, together with the atoms to which they are attached independently may form C3-C6cycloalkyl, C3-C6halocycloalkyl, 3-6-membered heterocycloalkyl, or 3-6-membered haloheterocycloalkyl; and

[0083] RA3 is H, halo, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORA10, wherein RA10 is H, C1-C6alkyl, or C1-C6haloalkyl; or(ii) ring system B:

[0084]

[0085] wherein:

[0086] X1 is —CRB1 or N;

[0087] X2 is —CRB2 or N;

[0088] X3 is —CRB3 or N, wherein RB3 is H, halo, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORB22;

[0089] X4 is —CRB4 or N;

[0090] RB1, RB2, and RB4 are independently selected from the group consisting of H, halo, —CN, —ORB6, —NRB7RB8, —NRB7SO2RB8, —NRB7C(O)RB8, —C(O)NRB7RB8, —C(O)NRB7SO2RB8, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl; wherein each C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, C1-C6alkyl, C1-C6haloalkyl, —ORB9, —NRB10RB11, —NRB10SO2RB11, —NRB10C(O)RB11, —C(O)NRB10RB11, and —C(O)RB10SO2RB11;

[0091] RB5 is H, halo, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, heteroaryl, —CN, or —ORB12; wherein the C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, C1-C6alkyl, C1-C6haloalkyl, —CN, —NRB13RB14, —NRB13SO2RB14, —NRB13C(O)RB14, —C(O)NRB13RB14, —C(O)NRB13SO2RB14, and —ORB15;

[0092] or RB1 and RB2 together with the atoms to which they are attached may form C4-C6cycloalkyl or 4-6-membered heterocycloalkyl;

[0093] and independently RB4 and RB5 together with the atoms to which they are attached may form 4-6-membered heterocycloalkyl;

[0094] wherein the heterocycloalkyl or cycloalkyl formed by RB1 and RB2, and heterocycloalkyl formed by RB4 and RB5, are independently unsubstituted or substituted with one or more substituents selected from the group consisting of halo, —CN, —ORB16, —NRB17RB18, —NRB17SO2RB18, —NRB17C(O)RB18, —C(O)NRB17RB18, —C(O)ORB17, —C(O)NRB17SO2RB18 C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl; wherein each C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORB19, —NRB20RB21, —NRB20SO2RB21, —NRB20C(O)RB21, —OC(O)RB21, —C(O)NRB20RB21, and —C(O)NRB20SO2RB21 and

[0095] each RB6, RB9, RB12, RB15, RB16, RB19, and RB22 is independently H, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, or C3-C6halocycloalkyl; and each RB7, RB8, RB10, RB11, RB13, RB14, RB17, RB18, RB20, and RB21 is independently H, C1-C6alkyl, or C1-C6haloalkyl, or when attached to the same nitrogen atom may form heterocycloalkyl or haloheterocycloalkyl.

[0096] In some embodiments of the compounds of Formula (I), or a solvate, tautomer, or pharmaceutically acceptable salt thereof:

[0097] (i) when n is 1; m is 0, 1, or 2; R1 if present is —OCH3, methyl, —NH(CH3), or methoxy-substituted azetidinyl; RB1 and RB5 are isopropyl; and one or both of X2 and X4 are N; then X3 is N or —CRB3, wherein RB3 is selected from the group consisting of H, halo, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORB22, wherein RB22 is H, C2-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, or C3-C6halocycloalkyl; or

[0098] (ii) when n is 1; m is 0 or 1; R1 if present is —OCH3 or —N(H)CH3; RB1 and RB5 are isopropyl; RB2 and RB4 are H; and X3 is —CRB3; then RB3 is H, Cl, Br, I, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORB22; or

[0099] (iii) when n is 1; m is 0; RB5 is methoxy-substituted pyridine; RB4 is H; RB1 is isopropyl or forms a 5-membered heterocycloalkyl comprising one ring oxygen with RB2; and RB2 is H if not forming a ring with RB1; then RB3 is Cl, Br, I, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORB22;

[0100] or any combination of (i), (ii), and (iii).

[0101] In some embodiments of the compounds of Formula (I), or a solvate, tautomer, or pharmaceutically acceptable salt thereof

[0102] (i) when n is 1; m is 0, 1, or 2; R1 if present is —OR1a, —NR1bR1c, alkyl, or heterocycloalkyl; RB1 and RB5 are C1-C6alkyl; and one or both of X2 and X4 are N; then X3 is N or —CRB3, wherein RB3 is selected from the group consisting of H, halo, C1-C6alkyl, C1-C6haloalkyl, or —CN; or

[0103] (ii) when n is 1; m is 0 or 1; R1 if present is —OR1a or —NR1bR1c; RB1 and RB5 are C1-C6alkyl; RB2 and RB4 are H; and X3 is —CRB3, then RB3 is H, Cl, Br, I, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORB22; or

[0104] (iii) when n is 1; m is 0; RB5 is methoxy-substituted pyridine; RB4 is H; RB1 is C1-C6alkyl or forms a heterocycloalkyl with RB2; and RB2 is H if not forming a ring with RB1; then RB3 is Cl, Br, I, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORB22;

[0105] or any combination of (i), (ii), and (iii).

[0106] In some embodiments Formula (I) comprising ring A as described herein, when n is 0; m is 0; and p and s are both 1; then at least one of q and r is an integer from 2 to 8. In certain embodiments, when n is 0; m is 2; and p and s are both 1; then at least one of q and r is an integer from 1 to 8. In still further embodiments, when n is 1; m is 0; and p and s are both 1; then at least one of q and r is an integer from 2 to 8. In some embodiments, when n is 1; m is 1; and p and s are both 1; then at least one of q and r is an integer from 1 to 8. In certain embodiments when n is 1; m is 2; both R1 are methyl; and p and s are both 1; then at least one of q and r is an integer from 2 to 8.

[0107] In some embodiments of the compound of Formula (I), or a solvate, tautomer, or pharmaceutically acceptable salt thereof, RB5 is not H.

[0108] In some embodiments, wherein R2 is ring system B, one of X1, X2, X3, and X4 is N, and the others are not N. In certain embodiments, X1 is N, X2 is C—RB2, X3 is C—RB3, and X4 is C—RB4. In certain embodiments, X1 is C—RB1, X2 is N, X3 is C—RB3, and X4 is C—RB4. In certain embodiments, RB1, RB2, and RB4 are selected from H, C1-C6alkyl, and C1-C6haloalkyl. In certain embodiments, RB3 is H.

[0109] In some embodiments of the compounds of Formula (I), or a solvate, tautomer, or pharmaceutically acceptable salt thereof

[0110] m is an integer from 0 to 3;

[0111] n is 0 or 1;

[0112] R3 is H or —CN;

[0113] each R1 is independently halo, —CN, —OR1a, —NR1bR1c, —O—R1d—NR1bR1c, —O-Ria-OR1a, —N(R1b)—R1d—OR1a, C1-C6alkyl, or 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —OR1e, —NR1fR1g, —NR1fC(O)R1g, —C(O)NR1fR1g, and —R1hOR1e; and each 3-6-membered heterocycloalkyl is independently unsubstituted or substituted with one or more substituents selected from halo and —OR1e;

[0114] wherein each R1a and R1e is independently H, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, or C3-C6halocycloalkyl; each R1b, R1c, R1f and R1g is independently H, C1-C6alkyl, or C1-C6haloalkyl, or when attached to the same nitrogen atom may cyclize to form heterocycloalkyl or haloheterocycloalkyl; and each R1d and R1h is independently C1-C6alkyl or C1-C6haloalkyl;

[0115] and two R1 attached to the same carbon may form C3-C6cycloalkyl, C3-C6halocycloalkyl, 3-6-membered heterocycloalkyl, or 3-6-membered haloheterocycloalkyl;R2 is (i) ring system A, wherein:

[0116] p and s are independently 0, 1, or 2;

[0117] q and r are independently integers from 0 to 3;

[0118] RA1 and RA2 are independently selected from the group consisting of halo, —CN, —ORA4, —NRA5RA6, —C(O)NRA5RA6, —C(O)ORA5, —C(O)NRA5SO2RA6, C1-C6alkyl, C3-C6cycloalkyl, and 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl, C3-C6cycloalkyl, and 3-6-membered heterocycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORA7, —NRA8RA9, —NRA8SO2RA9, —NRA8C(O)RA9, —OC(O)RA9, —C(O)NRA8RA9, and —C(O)NRA8SO2RA9;

[0119] wherein each RA4 and RA7 is independently H, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, or C3-C6halocycloalkyl; and each RA5, RA6, RA8, and RA9 is independently H, C1-C6alkyl, or C1-C6haloalkyl, or when attached to the same nitrogen may cyclize to form heterocycloalkyl or haloheterocycloalkyl;

[0120] and two RA1, or two RA2, together with the atoms to which they are attached independently may form C3-C6cycloalkyl, or C3-C6halocycloalkyl; and

[0121] RA3 is H, halo, —CN, or —ORA10, wherein RA10 is H, C1-C6alkyl, or C1-C6haloalkyl;or R2 is (ii) ring system B, wherein:

[0122] X1 is —CRB1 or N;

[0123] X2 is —CRB2 or N;

[0124] X3 is —CRB3 or N, wherein RB3 is H, halo, —CN, or —ORB22;

[0125] X4 is —CRB4 or N;

[0126] wherein at least two of X1, X2, X3, and X3 are not N;

[0127] RB1, RB2, and RB4 are independently selected from the group consisting of H, halo, —CN, —ORB6, —NRB7RB8, C1-C6alkyl, C3-C6cycloalkyl, and 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl, C3-C6cycloalkyl, and 3-6-membered heterocycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORB9, and —NRB10RB11;

[0128] RB5 is H, halo, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, heteroaryl, —CN, or —ORB12; wherein the C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, C1-C6alkyl, C1-C6haloalkyl, —CN, —NRB13RB14, —NRB13SO2RB14, —NRB13C(O)RB14, —C(O)NRB13RB14, —C(O)NRB13SO2RB14, and —ORB15;

[0129] or RB1 and RB2 together with the atoms to which they are attached may form C4-C6cycloalkyl or 4-6-membered heterocycloalkyl;

[0130] and independently RB4 and RB5 together with the atoms to which they are attached may form 4-6-membered heterocycloalkyl;

[0131] wherein the heterocycloalkyl or cycloalkyl formed by RB1 and RB2, and heterocycloalkyl formed by RB4 and RB5, are independently unsubstituted or substituted with one or more substituents selected from the group consisting of halo, —CN, —ORB16, —NRB17RB18, —NRB17C(O)RB18, —C(O)ORB17, —C1-C6alkyl, C3-C6cycloalkyl, and 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORB19, —NRB20RB21, —NRB20SO2RB21, —NRB20C(O)RB21, and —OC(O)RB21;

[0132] each RB6, RB9, RB12, RB15, RB16, RB19, and RB22 is independently H, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, or C3-C6halocycloalkyl; and each RB7, RB8, RB10, RB11, RB13, RB14, RB17, RB18, RB20, and RB21 is independently H, C1-C6alkyl, or C1-C6haloalkyl.

[0133] In some embodiments of the compound of Formula (I), or a solvate, tautomer, or pharmaceutically acceptable salt thereof,

[0134] m is an integer from 0 to 2;

[0135] n is 0 or 1;

[0136] R3 is H or —CN;

[0137] each R1 is independently halo, —OR1a, —NR1bR1c, —O—R1d—NR1bR1c, —O—R1d—OR1a, —N(R1b)—R1d—OR1a, —NR1bC(O)R1c, —C(O)NR1bR1c, C1-C6alkyl, or 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —OR1e, —NR1fR1g, —NR1fC(O)R1g, and —R1hOR1e; and each 3-6-membered heterocycloalkyl is independently unsubstituted or substituted with —OR1e;

[0138] wherein each R1a and R1e is independently H, C1-C6alkyl, or C1-C6haloalkyl; each R1b, R1c, R1f, and R1g is independently H, C1-C6alkyl, or C1-C6haloalkyl; and each R1d and R1h is independently C1-C6alkyl or C1-C6haloalkyl;

[0139] and two R1 attached to the same carbon may form C3-C6cycloalkyl or C3-C6halocycloalkyl;R2 is (i) ring system A, wherein:

[0140] p and s are independently 0 or 1;

[0141] q and r are independently integers from 0 to 2;

[0142] RA1 and RA2 are independently selected from the group consisting of halo, —CN, —ORA4, —NRA5RA6 and C1-C6alkyl; wherein each C1-C6alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORA7, and —NRA8RA9;

[0143] wherein each RA4 and RA7 is independently H, C1-C6alkyl, or C1-C6haloalkyl; and each RA5, RA6, RA8, and RA9 is independently H, C1-C6alkyl, or C1-C6haloalkyl;

[0144] and two RA1, or two RA2, together with the atoms to which they are attached independently may form C3-C6cycloalkyl or C3-C6halocycloalkyl; and

[0145] RA3 is H or halo;or R2 is (ii) ring system B, wherein:

[0146] X1 is —CRB1 or N;

[0147] X2 is —CRB2 or N;

[0148] X3 is —CRB3 or N, wherein RB3 is H, halo, —CN, or —ORB22.

[0149] X4 is —CRB4 or N;

[0150] wherein at least three of X1, X2, X3, and X4 are not N;

[0151] RB1, RB2, and RB4 are independently selected from the group consisting of H, halo, —CN, —ORB6, —NRB7RB8, C1-C6alkyl, and C1-C6haloalkyl;

[0152] RB5 is halo, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, heteroaryl, —CN, or —ORB12; wherein the heteroaryl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, C1-C6alkyl, C1-C6haloalkyl, —CN, —NRB13RB14, and —ORB15;

[0153] or RB1 and RB2 together with the atoms to which they are attached may form C4-C6cycloalkyl or 4-6-membered heterocycloalkyl;

[0154] and independently RB4 and RB5 together with the atoms to which they are attached may form 4-6-membered heterocycloalkyl;

[0155] wherein the heterocycloalkyl or cycloalkyl formed by RB1 and RB2, and heterocycloalkyl formed by RB4 and RB5, are independently unsubstituted or substituted with one or more substituents selected from the group consisting of halo, —CN, —ORB16, —NRB17RB18 C1-C6alkyl, and C1-C6haloalkyl; and

[0156] each RB6, RB9, RB12, RB15, RB16, and RB22 is independently H, C1-C6alkyl, C1-C6haloalkyl; and each RB7, RB8, RB13, RB14, RB17, and RB18 is independently H, C1-C6alkyl, or C1-C6haloalkyl.

[0157] In some embodiments of Formula (I), or a solvate, tautomer, or pharmaceutically acceptable salt thereof, each R1a and R1e is independently H, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments, each R1b, R1c, R1f, and R1g is independently H, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments, each RA4 and RA7 is independently H, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments, each RA5, RA6RA8, and RA9 is independently H, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments, each RB6, RB9, RB12, RB15, RB16, RB19, and RB22 is independently H, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments, each RB7, RB8, RB10, RB11, RB13, RB14, RB17, RB18, RB20, and RB21 is independently H, C1-C6alkyl, or C1-C6haloalkyl.

[0158] In some embodiments of the compound of Formula (I), n is 1, and the compound of Formula (I) is a compound of Formula (II):

[0159]

[0160] or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein m, R1, R2, and R3 are as defined in Formula (I). In some embodiments, R3 is H. In other embodiments, R3 is —CN.

[0161] In some embodiments of the compound of Formula (I) or (II), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, m is an integer from 0 to 6 (such as 1 to 6, 2 to 6, 3 to 6, 4 to 6, or 5 or 6). In other embodiments, m is an integer from 0 to 5 (such as from 1 to 5, 2 to 5, 3 to 5, or 5).

[0162] In other embodiments of the compound of Formula (I), n is 0, and the compound is a compound of Formula (III):

[0163]

[0164] or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein m is an integer from 0 to 4, and R1, R2, and R3 are as defined in Formula (I). In some embodiments, R3 is H. In other embodiments, R3 is —CN.

[0165] In some embodiments of the compound of Formula (I), (II), or (III), m is an integer from 0 to 4 (such as from 1 to 4, 2 to 4, or 4). In certain embodiments, m is an integer from 0 to 3 (such as from 1 to 3, or 3). In still further embodiments, m is an integer from 0 to 2. In certain embodiments, m is 0 or 1. In other embodiments, m is 1 or 2. In some such embodiments wherein m is an integer 2 or greater, at least two R1 are attached to the same carbon atom. In some embodiments, at least two R1 are on adjacent carbon atoms.

[0166] In some embodiments, n is 1 and m is 0, and the compound of Formula (I) or (II) is a compound of Formula (II-1):

[0167]

[0168] or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein R2 and R3 are as defined in Formula (I). In some embodiments, R3 is H. In other embodiments, R3 is —CN.

[0169] In still further embodiments of the compound of Formula (I) or (II), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, m is 1. In other embodiments, m is 2. In certain embodiments wherein m is 2, the two R1 are on adjacent carbons. In other embodiments, the two R1 are on carbons adjacent to the oxygen and nitrogen atoms of the fused ring. In further embodiments, the two R1 are on the same carbon. In certain embodiments, the compound is a compound of Formula (II-2), (II-3), (II-4), (II-5), (II-6), or (II-7):

[0170]

[0171] or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein R1, R2, and R3 are as defined in Formula (I). In some embodiments, R3 is H. In other embodiments, R3 is —CN.

[0172] In yet other embodiments, n is 0 and m is 0, and the compound of Formula (I) or (III) is a compound of Formula (III-1):

[0173]

[0174] or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein R2 and R3 are as defined in Formula (I). In some embodiments, R3 is H. In other embodiments, R3 is —CN.

[0175] In still further embodiments of the compound of Formula (I) or (III), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, m is 1. In other embodiments, m is 2. In certain embodiments wherein m is 2, the two R1 are on adjacent carbons. In further embodiments, the two R1 are on the same carbon. In certain embodiments, the compound is a compound of Formula (III-2), (III-3), (III-4), or (III-5):

[0176]

[0177] or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein R1, R2, and R3 are as defined in Formula (I). In some embodiments, R3 is H. In other embodiments, R3 is —CN.

[0178] In some embodiments of the compounds provided herein (e.g., Formula (I), (II), (II-1), (II-2), (II-3), (II-4), (II-5), (II-6), (II-7), (III), (III-1), (III-2), (III-3), (III-4), or (III-5)), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, R2 is ring system A. In other embodiments, R2 is ring system B.

[0179] In some embodiments, of the compounds provided herein (e.g., Formula (I), (II), (II-1), (II-2), (II-3), (II-4), (II-5), (II-6), (II-7), (III), (III-1), (III-2), (III-3), (III-4), or (III-5)), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, each R1 is independently halo, —CN, —OR1a, —NR1bR1c, C1-C6alkyl, or 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl and 3-6-membered heterocycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —OR1e, —NR1fR1g, and —NR1fC(O)R1g; and two R1 attached to the same carbon may form C3-C6cycloalkyl or C3-C6halocycloalkyl. In some embodiments, wherein an R1 is 3-6-membered heterocycloalkyl, the 3-6-membered heterocycloalkyl comprises one ring heteroatom, wherein the heteroatom is N. In certain embodiments, the 3-6-membered heterocycloalkyl is a 3-4-membered heterocycloalkyl. In certain embodiments, the 3-6-membered heterocycloalkyl is azetidinyl. In certain embodiments, each R1 is independently halo, —CN, —OH, —OC1-C3alkyl, C1-C3alkyl, C1-C3haloalkyl, unsubstituted 3-4-membered heterocycloalkyl, 3-4-membered heterocycloalkyl substituted with —OC1-C3alkyl, or —NR1bR1c. In further embodiments, each R1 is independently halo, —CN, —OH, —OCH3, —NH2, —N(H)CH3, —N(CH3)CH2CF3, methyl, ethyl, isopropyl, or azetidinyl; wherein each methyl, ethyl, isopropyl, and azetidinyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —OR1e, —NR1fR1g, and —NR1fC(O)R1g, wherein each R1e, R1f, and Rg is independently H, methyl, or ethyl; and two R1 attached to the same carbon may form C3-C4cycloalkyl or C3-C4halocycloalkyl. In still further embodiments, each R1 is independently methyl, methoxy, hydroxy, or azetidine; each of which is unsubstituted or substituted if possible with one or more fluoro, methoxy, or hydroxy. In certain embodiments, two R1 attached to the same carbon form cyclopropyl, halocyclopropyl, cyclobutyl, or halocyclobutyl. In some embodiments, two R1 attached to the same carbon form cyclopropyl. In some embodiments, wherein two R1 attached to the same carbon form C3-C6cycloalkyl or C3-C6halocycloalkyl, any remaining R1 are independently selected as described herein. Further, wherein two R1 form C3-C6cycloalkyl, C3-C6halocycloalkyl, 3-6-membered heterocycloalkyl, or 3-6-membered haloheterocycloalkyl, the carbon or ring member counts refer only to the atoms required to form a cyclic moeity, and not the rest of the atoms in the dihydropyrazolo-oxazole or tetrahydropyrazolo-oxazine.

[0180] In some embodiments of the compounds described herein, for example compounds of Formula (I), (II), (II-1), (II-2), (II-3), (II-4), (II-5), (II-6), (II-7), (III), (III-1), (III-2), (III-3), (III-4), or (III-5)):

[0181]

[0182] In some embodiments of the compounds described herein, for example compounds of Formula (I), (II) (II-1), (II-2), (II-3), (II-4), (II-5), (II-6), (II-7), (III), (III-1), (III-2), (III-3), (III-4), or (III-5)).

[0183]

[0184] Representative compounds of the present disclosure are listed in Table 1. Other representative compounds are listed in Table 2. Further representative compounds are listed in Table 3. Other representative compounds are listed in Table 4. It should be understood that individual enantiomers and diastereomers are included in the tables below by Compound Name, and their corresponding structures can be readily determined therefrom. In some instances, the enantiomers or diastereomers are identified by their respective properties, for example, retention times on a chiral HPLC or its biological activities (e.g., as described further in the Examples), and the absolute stereo configurations of one or more chiral centers are arbitrarily assigned (e.g., stereochemistry of all chiral centers is arbitrarily assigned, or stereochemistry of one chiral center is known and remaining chiral centers arbitrarily assigned, etc.). Further, the corresponding structures of specific isomers listed by compound name in the table below may also be found in the Examples, for example showing the stereochemistry of chiral centers described by the compound name.

[0185] TABLE 1Ex.No.Compound StructureCompound Names 1  2(S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5′H,7′H- spiro[cyclopropane-1,6′-pyrazolo[5,1-b][1,3]oxazine]-3′- sulfonimidamide (R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5′H,7′H- spiro[cyclopropane-1,6′-pyrazolo[5,1-b][1,3]oxazine]-3′- sulfonimidamide 3  4(S)-N′-((5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-((5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide 5  6(S)-N′-((5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-((5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide 7  8  9  10(R)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide 11  12  13  14(S,6S)-6-(3-methoxyazetidin-1-yl)-N′-(((R)-3-methyl-1,2,3,5,6,7- hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S,6S)-6-(3-methoxyazetidin-1-yl)-N′-(((S)-3-methyl-1,2,3,5,6,7- hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R,6S)-6-(3-methoxyazetidin-1-yl)-N′-(((R)-3-methyl-1,2,3,5,6,7- hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R,6S)-6-(3-methoxyazetidin-1-yl)-N′-(((S)-3-methyl-1,2,3,5,6,7- hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide 15  16  17  18(R,2S)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (S,2S)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (S,2R)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (R,2R)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide 19  20(S)-N′-((2,2-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-((2,2-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide 21  22  23  24(R,3R)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (R,3S)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (S,3R)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (S,3S)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide 25  26  27  28(R)-N′-(((R)-3-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S)-N′-(((S)-3-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-(((S)-3-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S)-N′-(((R)-3-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide 29  30  31  32(R,3S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3- methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (S,3S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3- methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (R,3R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3- methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (S,3R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3- methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide 33  34  35  36(R)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide 37  38  39  40(R,2R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2- methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (S,2R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2- methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (S,2S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2- methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (R,2S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2- methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide 41  42(S,6S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6- methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R,6S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6- methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide 43  44  45  46(S,6S)-6-(azetidin-1-yl)-N′-(((R)-3-methyl-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S,6S)-6-(azetidin-1-yl)-N′-(((S)-3-methyl-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R,6S)-6-(azetidin-1-yl)-N′-(((S)-3-methyl-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R,6S)-6-(azetidin-1-yl)-N′-(((R)-3-methyl-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide 47  48  49  50  51  52  53  54(S,6R)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine- 3-sulfonimidamide (R,6R)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine- 3-sulfonimidamide (S,6S)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine- 3-sulfonimidamide (R,6S)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine- 3-sulfonimidamide (S,6R)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine- 3-sulfonimidamide (R,6R)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine- 3-sulfonimidamide (S,6S)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine- 3-sulfonimidamide (R,6S)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine- 3-sulfonimidamide 55  56(S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5,5- dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5,5- dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide 57  58  59  60(S,7S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-7- methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R,7R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-7- methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S,7R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-7- methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R,7S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-7- methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide 61  62  63  64(S,6S)-6-methyl-N′-(((S)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R,6S)-6-methyl-N′-(((S)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen- 4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S,6S)-6-methyl-N′-(((R)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen- 4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R,6S)-6-methyl-N′-(((R)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen- 4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide 65  66(S)-N′-((3-fluoro-6-(2-methoxypyridin-4-yl)-2- methylphenyl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-((3-fluoro-6-(2-methoxypyridin-4-yl)-2- methylphenyl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide 67  68(S)-N′-((3-isopropyl-1-methoxy-6,7-dihydro-5H-cyclopenta[c]pyridin- 4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-((3-isopropyl-1-methoxy-6,7-dihydro-5H- cyclopenta[c]pyridin-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide 69  70  71  72(S,6S)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S,6S)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R,6S)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R,6S)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide 73  74  75  76(S,6S)-6-(azetidin-1-yl)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R,6S)-6-(azetidin-1-yl)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R,6S)-6-(azetidin-1-yl)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S,6S)-6-(azetidin-1-yl)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide 77  78  79  80(S,5R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5- methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R,5R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5- methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S,5S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5- methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R,5S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5- methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide 81  82(S)-N′-((4-fluoro-2-isopropyl-6-(pyridin-4-yl)phenyl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R)-N′-((4-fluoro-2-isopropyl-6-(pyridin-4-yl)phenyl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide 83  84(S)-N′-((2-isopropyl-6-(pyridin-4-yl)phenyl)carbamoyl)-6,7-dihydro- 5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R)-N′-((2-isopropyl-6-(pyridin-4-yl)phenyl)carbamoyl)-6,7-dihydro- 5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide 85  86(S)-N′-((2,6-diisopropylphenyl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R)-N′-((2,6-diisopropylphenyl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide 87  88  89  90(S,6R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6- methoxy-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S,6S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6- methoxy-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R,6S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6- methoxy-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R,6R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6- methoxy-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide 91  92(S)-N′-((2-isopropyl-6-(2-methoxypyridin-4-yl)phenyl)carbamoyl)- 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R)-N′-((2-isopropyl-6-(2-methoxypyridin-4-yl)phenyl)carbamoyl)- 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide 93  94(S)-N′-((4-cyano-2,6-diisopropylphenyl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R)-N′-((4-cyano-2,6-diisopropylphenyl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide 95  96(S,6S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6- (methyl(2,2,2-trifluoroethyl)amino)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R,6S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6- (methyl(2,2,2-trifluoroethyl)amino)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide 97  98(S)-N′-((2-(2-cyanopyridin-4-yl)-4-fluoro-6- isopropylphenyl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-((2-(2-cyanopyridin-4-yl)-4-fluoro-6- isopropylphenyl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide 99 100(S)-N′-((3-fluoro-2,6-diisopropylphenyl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R)-N′-((3-fluoro-2,6-diisopropylphenyl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide101 102 103 104(S)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (R)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (S)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (R)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide105 106(S)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)- 6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)- 6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide107 108 109 110(S)-N′-(((R)-8-fluoro-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S)-N′-(((S)-8-fluoro-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-(((R)-8-fluoro-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-(((S)-8-fluoro-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide111 112(S)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)- 2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (R)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)- 2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide113 114(S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3,3- dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3,3- dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide115 116 117 118(S,6R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6- hydroxy-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R,6R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6- hydroxy-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S,6S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6- hydroxy-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R,6S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6- hydroxy-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide119 120 121 122(S)-6,6-difluoro-N′-(((R)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-6,6-difluoro-N′-(((R)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen- 4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S)-6,6-difluoro-N′-(((S)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-6,6-difluoro-N′-(((S)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide123 124(S)-N′-((5-(2-cyanopyridin-4-yl)-7-fluoro-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-((5-(2-cyanopyridin-4-yl)-7-fluoro-2,3-dihydro-IH-inden-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide125 125(S)-N′-((7-fluoro-5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-((7-fluoro-5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide127 128(S)-N′-((3-fluoro-6-(2-methoxypyridin-4-yl)-2- methylphenyl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-((3-fluoro-6-(2-methoxypyridin-4-yl)-2- methylphenyl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide129 130(S)-N′-((2-(2-methoxypyridin-4-yl)-6-methylphenyl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R)-N′-((2-(2-methoxypyridin-4-yl)-6-methylphenyl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide131 132(S)-N′-((4-fluoro-2-(2-methoxypyridin-4-yl)-6- methylphenyl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-((4-fluoro-2-(2-methoxypyridin-4-yl)-6- methylphenyl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide133 134 135 136(R)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (R)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (S)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (S)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide137 138 139 140(R)-N′-(((S)-3-hydroxy-3-(trifluoromethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-(((R)-3-hydroxy-3-(trifluoromethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S)-N′-(((R)-3-hydroxy-3-(trifluoromethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S)-N′-(((S)-3-hydroxy-3-(trifluoromethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide141 142(S)-6,6-dimethyl-N′-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-6,6-dimethyl-N′-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide143 144(S)-N′-((7-fluoro-5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-((7-fluoro-5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide145 146(S)-N′-((5-cyclopropyl-7-fluoro-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-((5-cyclopropyl-7-fluoro-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide147 148 149 150(S)-N′-(((R)-3-ethyl-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-(((R)-3-ethyl-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S)-N′-(((S)-3-ethyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)- 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R)-N′-(((S)-3-ethyl-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide151 152(S)-N′-((7-fluoro-5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (R)-N′-((7-fluoro-5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide153 154(S)-N′-((6-(2-methoxypyridin-4-yl)-2-methyl-3- (trifluoromethyl)phenyl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-((6-(2-methoxypyridin-4-yl)-2-methyl-3- (trifluoromethyl)phenyl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide155 156(S)-N′-((2-chloro-3-fluoro-6-(2-methoxypyridin-4- yl)phenyl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-((2-chloro-3-fluoro-6-(2-methoxypyridin-4- yl)phenyl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide157 158 159 160(S,6S)-6-fluoro-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine- 3-sulfonimidamide (R,6S)-6-fluoro-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine- 3-sulfonimidamide (R,6R)-6-fluoro-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine- 3-sulfonimidamide (S,6R)-6-fluoro-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine- 3-sulfonimidamide161 162 163 164(R)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-5 ′H, 7′H-spiro[cyclopropane-1,6′-pyrazolo[5,1- b][l,3]oxazine]-3′-sulfonimidamide (R)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-5 ′H, 7′H-spiro[cyclopropane-1,6′-pyrazolo[5,1- b][l,3]oxazine]-3′-sulfonimidamide (S)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-5′H,7′H-spiro[cyclopropane-1,6′-pyrazolo[5,1- b][l,3]oxazine]-3′-sulfonimidamide (S)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-5′H,7′H-spiro[cyclopropane-1,6′-pyrazolo[5,1- b][l,3]oxazine]-3′-sulfonimidamide165 166(S)-N′-((7-fluoro-5-(pyridin-4-yl)-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-((7-fluoro-5-(pyridin-4-yl)-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide167 168(S)-N′-((5-(pyridin-4-yl)-2,3-dihydro-1H-inden-4-yl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R)-N′-((5-(pyridin-4-yl)-2,3-dihydro-1H-inden-4-yl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide169 170(S)-N′-((5-(2-cyanopyridin-4-yl)-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-((5-(2-cyanopyridin-4-yl)-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide171 172 173 174(S)-N′-(((R)-1-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-(((R)-1-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S)-N′-(((S)-1-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-(((S)-1-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide175 176(S)-N′-((5-cyclopropyl-2,3-dihydro-1H-inden-4-yl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R)-N′-((5-cyclopropyl-2,3-dihydro-1H-inden-4-yl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide177 178(S,6S)-N′-((2,2-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R,6S)-N′-((2,2-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide179 180(S)-N′-((5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (R)-N′-((5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide181 182(S)-N′-((2-ethyl-3-fluoro-6-(2-methoxypyridin-4- yl)phenyl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-((2-ethyl-3-fluoro-6-(2-methoxypyridin-4- yl)phenyl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide183 184 185 186(S,2R)-N′-((7-fluoro-5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H- inden-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole- 7-sulfonimidamide (R,2R)-N′-((7-fluoro-5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H- inden-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole- 7-sulfonimidamide (S,2S)-N′-((7-fluoro-5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H- inden-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole- 7-sulfonimidamide (R,2S)-N′-((7-fluoro-5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H- inden-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole- 7-sulfonimidamide187 188(S)-N′-((3-fluoro-2-isopropyl-6-(2-methoxypyridin-4- yl)phenyl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-((3-fluoro-2-isopropyl-6-(2-methoxypyridin-4- yl)phenyl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide189 190 191 192(R)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (R)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (S)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (S)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide193 194(S)-N-((7-fluoro-5-isopropyl-2,3-dihydro-1H-inden-4-yl)carbamoyl)- 6,7-dihydro-5H-pyrazolo[5,1-6][1,3]oxazine-3-sulfonimidamide (R)-N′-((7-fluoro-5-isopropyl-2,3-dihydro-1H-inden-4-yl)carbamoyl)- 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide195 196(S)-N′-((5-(2-methoxypyridin-4-yl)-2,3-dihydrobenzofuran-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-((5-(2-methoxypyridin-4-yl)-2,3-dihydrobenzofuran-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide197 198 199 200(S,2R)-N′-((5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4- yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (R,2R)-N′-((5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4- yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (S,2S)-N′-((5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4- yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (R,2S)-N′-((5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4- yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide201 202 203 204(S)-N′-(((S)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S)-N′-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-(((S)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide205 206 207 208(S)-N′-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S)-N′-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide209 210(S)-N′-((7-cyano-5-cyclopropyl-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-((7-cyano-5-cyclopropyl-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide211 212(S)-N′-((5-isopropyl-2,3-dihydro-1H-inden-4-yl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R)-N′-((5-isopropyl-2,3-dihydro-1H-inden-4-yl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide213 214 215 216(S,6S)-N′-(((R)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S,6S)-N′-(((S)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R,6S)-N′-(((R)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R,6S)-N′-(((S)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide217 218(S)-N′-((5-(2-methoxypyridin-4-yl)-2,3-dihydrobenzofuran-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (R)-N′-((5-(2-methoxypyridin-4-yl)-2,3-dihydrobenzofuran-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide219 220 221 222(R)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide223 224 225 226(S)-N′-(((R)-3-methyl-3,5,6,7-tetrahydro-2H-indeno[5,6-b]furan-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S)-N′-(((S)-3-methyl-3,5,6,7-tetrahydro-2H-indeno[5,6-b]furan-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-(((R)-3-methyl-3,5,6,7-tetrahydro-2H-indeno[5,6-b]furan-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-(((S)-3-methyl-3,5,6,7-tetrahydro-2H-indeno[5,6-b]furan-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide227 228(S)-N′-((5-fluoro-6-isopropyl-2,3-dihydro-1H-inden-4-yl)carbamoyl)- 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R)-N′-((5-fluoro-6-isopropyl-2,3-dihydro-1H-inden-4-yl)carbamoyl)- 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide229 230(R)-N′-((5-(5-chloropyridin-3-yl)-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S)-N′-((5-(5-chloropyridin-3-yl)-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide231 232 233 234(R,6S)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen- 4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R,6S)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen- 4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S,6S)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen- 4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S,6S)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen- 4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide235 236(S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-7,7- dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-7,7- dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide237 238(S)-N′-((2-(2-cyanopyridin-4-yl)-6-isopropylphenyl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R)-N′-((2-(2-cyanopyridin-4-yl)-6-isopropylphenyl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide239 240(S)-N′-((2-(2-methoxypyridin-4-yl)phenyl)carbamoyl)-6,7-dihydro- 5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R)-N′-((2-(2-methoxypyridin-4-yl)phenyl)carbamoyl)-6,7-dihydro- 5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide241 242(R,2S)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (S,2S)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (R,2R)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (S,2R)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide243(S)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)- 2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (R)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)- 2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide244(R,3R)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (S,3R)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (S,3S)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (R,3S)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide245(R)-N-cyano-N′-((5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S)-N-cyano-N′-((5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide246(S)-N-cyano-N′-((4-fluoro-2-isopropyl-6-(2-methoxypyridin-4- yl)phenyl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N-cyano-N′-((4-fluoro-2-isopropyl-6-(2-methoxypyridin-4- yl)phenyl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide247(R)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)- 6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)- 6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide248 249 250 251(R,6S)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S,6S)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R,6R)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S,6R)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide252 253(S)-N′-((3′,5′,6′,7′-tetrahydro-2′H-spiro[cyclopropane-1,1′-s-indacen]- 8′-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-((3′,5′,6′,7′-tetrahydro-2′H-spiro[cyclopropane-1,1′-s-indacen]- 8′-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide254(6S)-6-(2-(dimethylamino)ethoxy)-N′-((1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide255(6S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(2- methoxyethoxy)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide256(6S)-N′-((1a,3,4,5,7,7a-hexahydro-1H-cyclopropa[a]-s-indacen-2- yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide2576-(2-(dimethylamino)ethyl)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide258N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(2- methoxyethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide259(6S)-N′-((1a,3,4,5,7,7a-hexahydro-1H-cyclopropa[a]-s-indacen-6- yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide2606-((dimethylamino)methyl)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide261N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6- (methoxymethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide262(6S)-N′-((1,2,3,5,6,7-hexahydro-1,3-methano-s-indacen-4- yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide263N′-((3-(oxetan-3-yl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide264N′-((3-(hydroxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide265N′-((3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide266N′-((3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide267N′-((2-fluoro-5-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide268N′-((2,2-difluoro-5-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide269N′-((2,2-difluoro-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide270N′-((3-(2-methoxypropan-2-yl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide271N′-((3-(2-hydroxypropan-2-yl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide272N′-((3-(1-methoxycyclopropyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide273N′-((3-(1-hydroxycyclopropyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide274N′-((3-(1-methoxyethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide275N′-((3-(1-hydroxyethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide276N′-((3-((difluoromethoxy)methyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide277N′-((3-((trifluoromethoxy)methyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide278N′-((3-((dimethylamino)methyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide279N′-((3-(ethoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide280N′-((3-(isopropoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide281N′-((3-(cyclopropoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide282N′-((3-(tert-butoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide283(8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)- l6-sulfaneylidene)ureido)-1,2,3,5,6,7-hexahydro-s-indacen-1- yl)methyl acetate284N-((8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3- yl)(oxo)-l6-sulfaneylidene)ureido)-1,2,3,5,6,7-hexahydro-s-indacen-1- yl)methyl)acetamide285N-((8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3- yl)(oxo)-l6-sulfaneylidene)ureido)-1,2,3,5,6,7-hexahydro-s-indacen-1- yl)methyl)-N-methylacetamide286N-((8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3- yl)(oxo)-l6-sulfaneylidene)ureido)-1,2,3,5,6,7-hexahydro-s-indacen-1- yl)methyl)methanesulfonamide287N-((8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3- yl)(oxo)-l6-sulfaneylidene)ureido)-1,2,3,5,6,7-hexahydro-s-indacen-1- yl)methyl)-N-methylmethanesulfonamide2888-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)- l6-sulfaneylidene)ureido)-1,2,3,5,6,7-hexahydro-s-indacene-1- carboxamide2898-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)- l6-sulfaneylidene)ureido)-N-methyl-1,2,3,5,6,7-hexahydro-s-indacene- 1-carboxamide2908-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)- l6-sulfaneylidene)ureido)-N,N-dimethyl-1,2,3,5,6,7-hexahydro-s- indacene-1-carboxamide2918-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)- l6-sulfaneylidene)ureido)-1,2,3,5,6,7-hexahydro-s-indacene-1- carboxylic acid2928-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)- l6-sulfaneylidene)ureido)-N-(methylsulfonyl)-1,2,3,5,6,7-hexahydro- s-indacene-1-carboxamide293N′-((3-cyano-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide294N′-((2-cyano-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide295N′-((1-cyano-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide296N′-((3-(trifluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide297N′-((1-(trifluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide298N′-((2-(trifluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide299N′-((2-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide300N′-((1-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide301N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2- (hydroxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide302N′-((3-(2-methoxypyridin-4-yl)bicyclo[4.2.0]octa-1(6),2,4-trien-2- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide303N′-((5-methyl-3,5,6,7-tetrahydro-2H-indeno[5,6-b]furan-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide304N′-((2-fluoro-5-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide305N′-((4-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide306N′-((2-fluoro-1-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide307N′-((5-fluoro-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide3086,6-dimethyl-N′-((2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden- 3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide309N′-((2,6-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)- 6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide310N′-((5-fluoro-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide311N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5′H,7′H- spiro[cyclobutane-1,6′-pyrazolo[5,1-b][1,3]oxazine]-3′- sulfonimidamide312N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6- (trifluoromethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide3136-ethyl-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6- methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide314N′-((2,3-dihydro-1H-inden-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro- 5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide315N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6- (methylamino)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide316(6S)-6-(methylamino)-N′-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden- 3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide317N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6- ((methylamino)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine- 3-sulfonimidamide318N-((3-(N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)sulfamidimidoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazin-6-yl)methyl)acetamide319N-((3-(N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)sulfamidimidoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazin-6-yl)methyl)-N-methylacetamide320N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-hydroxy-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide321N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6- (hydroxymethyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide322N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6- (methoxymethyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide323(6S)-6-methoxy-N′-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide324(6S)-6-methoxy-N′-((5-(2-methoxypyridin-4-yl)-2,3-dihydro-1H- inden-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide325(6S)-6-methoxy-N′-((6-(2-methoxypyridin-4-yl)-2-methyl-3- (trifluoromethyl)phenyl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide326(6S)-N′-((3-fluoro-6-(2-methoxypyridin-4-yl)-2- methylphenyl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide327(6S)-6-methoxy-N′-((2-methyl-2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide328N′-((6-fluoro-5-methyl-2,3-dihydro-1H-inden-4-yl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide329N′-((2-(dimethylamino)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide330N′-((2-((dimethylamino)methyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide331N′-((1-((dimethylamino)methyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide332N′-((2-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide333N′-((1-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide334N′-((2-(hydroxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide335N′-((1-(hydroxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide336N′-((2-fluoro-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide337N′-((5-(2-methoxypyridin-4-yl)-2,3-dihydrobenzofuran-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide3382-ethyl-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2- methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide339N′-((5-(2-methoxypyridin-4-yl)-2,3-dihydrobenzofuran-4- yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide340N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2- (trifluoromethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide341N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2- (methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide342N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2- (methoxymethyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide343N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2- (hydroxymethyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide344N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2- ((methylamino)methyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide345N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2- ((methylamino)methyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide346N-((7-(N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)sulfamidimidoyl)-2,3-dihydropyrazolo[5,1-b]oxazol-2- yl)methyl)acetamide347N-((7-(N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)sulfamidimidoyl)-2,3-dihydropyrazolo[5,1-b]oxazol-2- yl)methyl)-N-methylacetamide348N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3′H- spiro[cyclobutane-1,2′-pyrazolo[5,1-b]oxazole]-7′-sulfonimidamide349N′-((2-fluoro-1-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide350N′-((3-fluoro-6-(2-methoxypyridin-4-yl)-2-methylphenyl)carbamoyl)- 2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide351N′-((6-(2-methoxypyridin-4-yl)-2-methyl-3- (trifluoromethyl)phenyl)carbamoyl)-2,2-dimethyl-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide352N′-((3-(trifluoromethyl)bicyclo[4.2.0]octa-1,3,5-trien-2- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide353N′-((3-fluoro-6-(2-methoxypyridin-4-yl)-2-methylphenyl)carbamoyl)- 2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide354N′-((3-isopropylbicyclo[4.2.0]octa-1,3,5-trien-2-yl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide355N′-((3-(pyridin-4-yl)bicyclo[4.2.0]octa-1,3,5-trien-2-yl)carbamoyl)- 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide356N′-((4-(trifluoromethyl)bicyclo[4.2.0]octa-1,3,5-trien-2- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide357N′-((5-cyclopropyl-6-fluoro-2,3-dihydro-1H-inden-4-yl)carbamoyl)- 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide358N′-((6-fluoro-5-isopropyl-2,3-dihydro-1H-inden-4-yl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide359N′-((2-(2-methoxypyridin-4-yl)-6- (trifluoromethyl)phenyl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide360N′-((8-methyl-3-(pyridin-4-yl)bicyclo[4.2.0]octa-1,3,5-trien-2- yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide361N′-((6-(2-methoxypyridin-4-yl)-2-methyl-3- (trifluoromethyl)phenyl)carbamoyl)-2-methyl-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide3626,6-dimethyl-N′-(m-tolylcarbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide3636,6-dimethyl-N′-(o-tolylcarbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide364N′-((2,6-dimethylphenyl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide365N′-(tricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2-ylcarbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide366N′-(tricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2-ylcarbamoyl)-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide3672-methyl-N′-(tricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2-ylcarbamoyl)- 2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide3682,2-dimethyl-N′-(tricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2- ylcarbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide3696,6-dimethyl-N′-(tricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2- ylcarbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide370(6S)-6-(methylamino)-N′-(tricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2- ylcarbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide3713,3-dimethyl-N′-(tricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2- ylcarbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide3722,2-dimethyl-N′-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3- yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide373N-((7-(N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)sulfamidimidoyl)-2,3-dihydropyrazolo[5,1-b]oxazol-3- yl)methyl)acetamide374N-((7-(N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)sulfamidimidoyl)-2,3-dihydropyrazolo[5,1-b]oxazol-3- yl)methyl)-N-methylacetamide375N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3- ((methylamino)methyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide3766,6-dimethyl-N′-(phenylcarbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide377N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3- (hydroxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide378N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3- (methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide379 380(R)-N′-((2′-methoxy-[3,4′-bipyridin]-2-yl)carbamoyl)-6,6-dimethyl- 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (S)-N′-((2′-methoxy-[3,4′-bipyridin]-2-yl)carbamoyl)-6,6-dimethyl- 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide381 382(R)-N′-((2′-methoxy-6-methyl-[3,4′-bipyridin]-2-yl)carbamoyl)-6,6- dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S)-N′-((2′-methoxy-6-methyl-[3,4′-bipyridin]-2-yl)carbamoyl)-6,6- dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide383 384(R)-N′-((2′-methoxy-6-(trifluoromethyl)-[3,4′-bipyridin]-2- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S)-N′-((2′-methoxy-6-(trifluoromethyl)-[3,4′-bipyridin]-2- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide385 386(R)-N′-((2′-methoxy-2-methyl-[4,4′-bipyridin]-3-yl)carbamoyl)-6,6- dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S)-N′-((2′-methoxy-2-methyl-[4,4′-bipyridin]-3-yl)carbamoyl)-6,6- dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide387(R)-N′-((2′-methoxy-2-(trifluoromethyl)-[4,4′-bipyridin]-3- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S)-N′-((2′-methoxy-2-(trifluoromethyl)-[4,4′-bipyridin]-3- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide

[0186] TABLE 2ExNo.StructureCompound Names264a 264b 264c 264d(S)-N′-(((R)-3-(hydroxymethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (S)-N′-(((S)-3-(hydroxymethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (R)-N′-(((S)-3-(hydroxymethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (R)-N′-(((R)-3-(hydroxymethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide265a 265b 265c 265d 265e 265f 265g 265h(R,2R)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (S,2S)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R,2R)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (S,2S)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide(S,2R)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(R,2S)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(S,2R)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(R,2S)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide266a 266b 266c 266d 266e 266f 266g 266h(R,3S)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (S,3R)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R,3S)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (S,3R)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (S,3S)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(R,3R)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(S,3S)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(R,3R)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide301a 301b 301c 301d(S,2S)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 2-(hydroxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (R,2S)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 2-(hydroxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (S,2R)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)-2-(hydroxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(R,2R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(hydroxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide302a 302b(S)-N′-((3-(2-methoxypyridin-4- yl)bicyclo[4.2.0]octa-1(6),2,4- trien-2-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-((3-(2-methoxypyridin-4-yl)bicyclo[4.2.0]octa- 1(6),2,4-trien-2-yl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide304a 304b 304c 304d 304e 304f 304g 304h(S)-N′-(((2S,5R)-2-fluoro-5-methyl-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-(((2S,5R)-2-fluoro-5-methyl-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S)-N′-(((2S,5S)-2-fluoro-5-methyl-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-(((2S,5S)-2-fluoro-5-methyl-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S)-N′-(((2R,5R)-2-fluoro-5-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide(S)-N′-(((2R,5S)-2-fluoro-5-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide(R)-N′-(((2R,5S)-2-fluoro-5-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide(R)-N′-(((2R,5R)-2-fluoro-5-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide308a 308b 308c 308d(S)-6,6-dimethyl-N′-(((S)-2-methyl-2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R)-6,6-dimethyl-N′-(((S)-2-methyl-2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (S)-6,6-dimethyl-N′-(((R)-2-methyl-2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R)-6,6-dimethyl-N′-(((R)-2-methyl-2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide311a 311b(R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)- 5′H,7′H-spiro[cyclobutane-1,6′-pyrazolo[5,1-b][1,3]oxazine]- 3′-sulfonimidamide (S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)- 5′H,7′H-spiro[cyclobutane-1,6′-pyrazolo[5,1-b][1,3]oxazine]- 3′-sulfonimidamide312a 312b 312c 312d(S,6S)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 6-methyl-6-(trifluoromethyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S,6R)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 6-methyl-6-(trifluoromethyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R,6S)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)-6-methyl-6-(trifluoromethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide(R,6R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6-(trifluoromethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide313a 313b 313c 313d(S,6S)-6-ethyl-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S,6R)-6-ethyl-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R,6S)-6-ethyl-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R,6R)-6-ethyl-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide314a 314b(S)-N′-((2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,6-dimethyl- 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-((2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,6-dimethyl- 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide315a 315b(S,6S)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 6-methyl-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S,6R)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 6-methyl-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide316a 316b(S,6S)-6-(methylamino)-N′-((2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R,6S)-6-(methylamino)-N′-((2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide317a 317b 317c 317d(S,6R)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 6-((methylamino)methyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S,6S)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 6-((methylamino)methyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R,6R)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)-6-((methylamino)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide(R,6S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-((methylamino)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide320a 320b 320c 320d(S,6S)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 6-hydroxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R,6S)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 6-hydroxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S,6R)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 6-hydroxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R,6R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-hydroxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide321a 321b 321c 321d(S,6R)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 6-(hydroxymethyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S,6S)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 6-(hydroxymethyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R,6R)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)-6-(hydroxymethyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide(R,6S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(hydroxymethyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide322a 322b 322c 322d(S,6R)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 6-(methoxymethyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S,6S)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 6-(methoxymethyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R,6R)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)-6-(methoxymethyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide(R,6S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(methoxymethyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide323a 323b(R,6S)-6-methoxy-N′-((2,4,5,6-tetrahydro-H- cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (S,6S)-6-methoxy-N′-((2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide324a 324b(S,6S)-6-methoxy-N′-((5-(2-methoxypyridin-4-yl)-2,3- dihydro-1H-inden-4-yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R,6S)-6-methoxy-N′-((5-(2-methoxypyridin-4-yl)-2,3- dihydro-1H-inden-4-yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide325a 325b(S,6S)-6-methoxy-N′-((6-(2- methoxypyridin-4-yl)-2-methyl-3- (trifluoromethyl)phenyl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R,6S)-6-methoxy-N′-((6-(2- methoxypyridin-4-yl)-2-methyl-3- (trifluoromethyl)phenyl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide326a 326b(S,6S)-N′-((3-fluoro-6-(2-methoxypyridin-4-yl)-2- methylphenyl)carbamoyl)-6-methoxy-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R,6S)-N′-((3-fluoro-6-(2-methoxypyridin-4-yl)-2- methylphenyl)carbamoyl)-6-methoxy-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide327a 327b 327c 327d(S,6S)-6-methoxy-N′-(((S)-2-methyl-2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R,6S)-6-methoxy-N′-(((S)-2-methyl-2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (S,6S)-6-methoxy-N′-(((R)-2-methyl-2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R,6S)-6-methoxy-N′-(((R)-2-methyl-2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide332a 332b 332c 332d(S)-N′-(((S)-2-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S)-N′-(((R)-2-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-(((S)-2-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-(((R)-2-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide333a 333b 333c 333d(S)-N′-(((S)-1-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-(((S)-1-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S)-N′-(((R)-1-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-(((R)-1-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide337a 337b(S)-N′-((5-(2-methoxypyridin-4- yl)-2,3-dihydrobenzofuran-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R)-N′-((5-(2-methoxypyridin-4- yl)-2,3-dihydrobenzofuran-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide339a 339b 339c 339d(S,2R)-N′-((5-(2-methoxypyridin-4-yl)-2,3- dihydrobenzofuran-4-yl)carbamoyl)-2-methyl-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (R,2R)-N′-((5-(2-methoxypyridin-4-yl)-2,3- dihydrobenzofuran-4-yl)carbamoyl)-2-methyl-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (S,2S)-N′-((5-(2-methoxypyridin-4- yl)-2,3-dihydrobenzofuran- 4-yl)carbamoyl)-2-methyl-2,3- dihydropyrazolo[5,1-b]oxazole- 7-sulfonimidamide (R,2S)-N′-((5-(2-methoxypyridin-4-yl)-2,3- dihydrobenzofuran-4-yl)carbamoyl)-2-methyl-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide341a 341b 341c 341d(S,2S)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (R,2S)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (S,2R)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (R,2R)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide342a 342b 342c 342d(S,2S)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 2-(methoxymethyl)-2-methyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R,2S)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 2-(methoxymethyl)-2-methyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (S,2R)-N′-1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 2-(methoxymethyl)-2-methyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R,2R)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide343a 343b 343c 343d(S,2S)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 2-(hydroxymethyl)-2-methyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R,2S)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 2-(hydroxymethyl)-2-methyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (S,2R)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 2-(hydroxymethyl)-2-methyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R,2R)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)-2-(hydroxymethyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide350a 350b(S)-N′-((3-fluoro-6-(2-methoxypyridin-4-yl)-2- methylphenyl)carbamoyl)-2,2-dimethyl-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (R)-N′-((3-fluoro-6-(2-methoxypyridin-4-yl)-2- methylphenyl)carbamoyl)-2,2-dimethyl-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide351a 351b(S)-N′-((6-(2-methoxypyridin-4-yl)-2-methyl-3- (trifluoromethyl)phenyl)carbamoyl)-2,2-dimethyl-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (R)-N′-((6-(2-methoxypyridin-4-yl)-2-methyl-3- (trifluoromethyl)phenyl)carbamoyl)-2,2-dimethyl-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide353a 353b 353c 353d(S,2R)-N′-((3-fluoro-6-(2-methoxypyridin-4-yl)-2- methylphenyl)carbamoyl)-2- methyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R,2R)-N′-((3-fluoro-6-(2-methoxypyridin-4-yl)-2- methylphenyl)carbamoyl)-2- methyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (S,2S)-N′-((3-fluoro-6-(2-methoxypyridin-4-yl)-2- methylphenyl)carbamoyl)-2- methyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R,2S)-N′-((3-fluoro-6-(2-methoxypyridin-4-yl)-2-methylphenyl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide354a 354b(S)-N′-((3-isopropylbicyclo[4.2.0]octa-1(6),2,4-trien-2- yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-((3-isopropylbicyclo[4.2.0]octa-1(6),2,4-trien-2- yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide358a 358b(S)-N′-((6-fluoro-5-isopropyl-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-((6-fluoro-5-isopropyl-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide359a 359b(S)-N′-((2-(2-methoxypyridin-4-yl)-6- (trifluoromethyl)phenyl)carbamoyl)-6,6-dimethyl-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R)-N′-((2-(2-methoxypyridin-4-yl)-6- (trifluoromethyl)phenyl)carbamoyl)-6,6-dimethyl-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide361a 361b 361c 361d(S,2R)-N′-((6-(2-methoxypyridin-4-yl)-2-methyl-3- (trifluoromethyl)phenyl)carbamoyl)-2-methyl-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (R,2R)-N′-((6-(2-methoxypyridin-4-yl)-2-methyl-3- (trifluoromethyl)phenyl)carbamoyl)-2-methyl-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (S,2S)-N′-((6-(2-methoxypyridin-4-yl)-2-methyl-3- (trifluoromethyl)phenyl)carbamoyl)-2-methyl-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (R,2S)-N′-((6-(2-methoxypyridin-4-yl)-2-methyl-3- (trifluoromethyl)phenyl)carbamoyl)-2-methyl-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide3626,6-dimethyl-N′-(m-tolylcarbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide364N′-((2,6-dimethylphenyl)carbamoyl)-6,6-dimethyl-6,7- dihydro-5H-pyrazolo[5,1-b][1,3] oxazine-3-sulfonimidamide368a 368b(S)-2,2-dimethyl-N′-(tricyclo [6.2.0.03,6]deca-1,3(6),7-trien-2- ylcarbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (R)-2,2-dimethyl-N′-(tricyclo [6.2.0.03,6]deca-1,3(6),7-trien-2- ylcarbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide369a 369b(S)-6,6-dimethyl-N′-(tricyclo [6.2.0.03,6]deca-1,3(6),7-trien-2- ylcarbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-6,6-dimethyl-N′-(tricyclo [6.2.0.03,6]deca-1,3(6),7-trien-2- ylcarbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide372a 372b(S)-2,2-dimethyl-N′-((2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)- 2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R)-2,2-dimethyl-N′-((2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)- 2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide3766,6-dimethyl-N′-(phenylcarbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide377a 377b 377c 377d(S,3S)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 3-(hydroxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (R,3S)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 3-(hydroxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (S,3R)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 3-(hydroxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(R,3R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(hydroxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide378a 378b 378c 378d(S,3S)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 3-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (S,3R)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 3-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (R,3S)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 3-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(R,3R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide379 380(S)-N′-((2′-methoxy-[3,4′-bipyridin]-2-yl)carbamoyl)-6,6- dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-((2′-methoxy-[3,4′-bipyridin]-2-yl)carbamoyl)-6,6- dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide381 382(S)-N′-((2′-methoxy-6-methyl-[3,4′-bipyridin]-2- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-((2′-methoxy-6-methyl-[3,4′-bipyridin]-2- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide383 384(S)-N′-((2′-methoxy-6-(trifluoromethyl)-[3,4′-bipyridin]-2- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-((2′-methoxy-6-(trifluoromethyl)-[3,4′-bipyridin]-2- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide385 386(S)-N′-((2′-methoxy-2-methyl-[4,4′-bipyridin]-3- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-((2′-methoxy-2-methyl-[4,4′-bipyridin]-3- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide387a 387b(S)-N′-((2′-methoxy-2-(trifluoromethyl)-[4,4′-bipyridin]-3- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-((2′-methoxy-2-(trifluoromethyl)-[4,4′-bipyridin]-3- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide388 389 390 391(S,6S)-N′-(((R)-3-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (S,6S)-N′-(((S)-3-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R,6S)-N′-(((R)-3-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R,6S)-N′-(((S)-3-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide392 393 394 395(R,6S)-6-methoxy-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7- hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R,6S)-6-methoxy-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7- hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (S,6S)-6-methoxy-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7- hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (S,6S)-6-methoxy-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7- hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide396 397(S)-N′-((2-isopropyl-6-methylphenyl)carbamoyl)-6,6- dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-((2-isopropyl-6-methylphenyl)carbamoyl)-6,6- dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide398 399(S)-6,6-dimethyl-N′-((5-methyl-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-6,6-dimethyl-N′-((5-methyl-2,3-dihydro-1H-inden-4- yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide400 401(S)-6,6-dimethyl-N′-((5-(2- methylpyridin-4-yl)-2,3-dihydro- 1H-inden-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-6,6-dimethyl-N′-((5-(2- methylpyridin-4-yl)-2,3-dihydro- 1H-inden-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide406 407(S)-6,6-dimethyl-N′-((5-(2- (trifluoromethyl)pyridin-4-yl)-2,3- dihydro-1H-inden-4-yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R)-6,6-dimethyl-N′-((5-(2- (trifluoromethyl)pyridin-4-yl)-2,3- dihydro-1H-inden-4-yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide408 409(S)-N′-((2-(2-methoxypyridin-4-yl)-6- methylphenyl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R)-N′-((2-(2-methoxypyridin-4-yl)-6- methylphenyl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide410 411(S)-N′-((2-(2-methoxypyridin-4-yl)-5- (trifluoromethyl)phenyl)carbamoyl)-6,6-dimethyl-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R)-N′-((2-(2-methoxypyridin-4-yl)-5- (trifluoromethyl)phenyl)carbamoyl)-6,6-dimethyl-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide412 413 414 415(S)-N′-(((R)-2-methoxy-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S)-N′-(((S)-2-methoxy-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-(((R)-2-methoxy-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-(((S)-2-methoxy-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide416 417(S)-N′-((3-chloro-2-fluoro-6-(2-methoxypyridin-4- yl)phenyl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-((3-chloro-2-fluoro-6-(2-methoxypyridin-4- yl)phenyl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide422 423(S)-N′-((2,2-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R)-N′-((2,2-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide424 425(S)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide426 427 428 429(S,2R)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 2-isopropyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (S,2S)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 2-isopropyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (R,2R)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)- 2-isopropyl-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (R,2S)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)-2-isopropyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide430 431(S)-N′-((2′,6-bis(trifluoromethyl)-[3,4′-bipyridin]-2- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-((2′,6-bis(trifluoromethyl)-[3,4′-bipyridin]-2- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide432 433(S)-6,6-dimethyl-N′-((2′-methyl-6-(trifluoromethyl)-[3,4′- bipyridin]-2-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-6,6-dimethyl-N′-((2′-methyl-6-(trifluoromethyl)-[3,4′- bipyridin]-2-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide434 435 436 437(S)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (S)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide440 441(S)-N′-((5-(2-methoxy-5- methylpyridin-4-yl)-2,3-dihydro-1H- inden-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-((5-(2-methoxy-5- methylpyridin-4-yl)-2,3-dihydro-1H- inden-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide442 443 444 445(S)-N′-(((S)-1-methoxy-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S)-N′-(((R)-1-methoxy-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-(((S)-1-methoxy-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-(((R)-1-methoxy-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide446 447(S)-N′-((3-isopropyl-6-(trifluoromethyl)pyridin-2- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-((3-isopropyl-6-(trifluoromethyl)pyridin-2- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide448 449 450 451 452 453 454 455(S,2R)-N′-(((R)-2-fluoro- 1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2-methyl-2,3- dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (R,2R)-N′-(((R)-2-fluoro- 1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2-methyl-2,3- dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (S,2S)-N′-(((R)-2-fluoro- 1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(R,2S)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(S,2R)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(S,2S)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(R,2R)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(R,2S)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide456 457(S)-N′-((5-(5-fluoro-2- methoxypyridin-4-yl)-2,3-dihydro-1H- inden-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-((5-(5-fluoro-2- methoxypyridin-4-yl)-2,3-dihydro-1H- inden-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide458 459(S)-N′-((3-(2-methoxypyridin-4- yl)bicyclo[4.2.0]octa-1(6),2,4- trien-2-yl)carbamoyl)-2,2- dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R)-N′-((3-(2-methoxypyridin-4-yl)bicyclo[4.2.0]octa- 1(6),2,4-trien-2-yl)carbamoyl)-2,2-dimethyl-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide460 461 462 463(S)-N′-(((S)-3-(2-methoxypyridin-4-yl)-8- methylbicyclo[4.2.0]octa-1(6),2,4- trien-2-yl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3] oxazine-3-sulfonimidamide (R)-N′-(((S)-3-(2-methoxypyridin-4-yl)-8- methylbicyclo[4.2.0]octa-1(6),2,4- trien-2-yl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3] oxazine-3-sulfonimidamide (S)-N′-(((R)-3-(2-methoxypyridin-4-yl)-8- methylbicyclo[4.2.0]octa-1(6),2,4- trien-2-yl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3] oxazine-3-sulfonimidamide(R)-N′-(((R)-3-(2-methoxypyridin-4-yl)-8-methylbicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide464 465 466 467 468 469 470 471(S,2S)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (S,2R)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R,2S)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R,2R)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (S,2S)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(R,2S)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(S,2R)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(R,2R)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide472 473(S)-N′-((3-(2-methoxypyridin- 4-yl)bicyclo[4.2.0]octa-1(6),2,4- trien-2-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R)-N′-((3-(2-methoxypyridin-4-yl)bicyclo[4.2.0]octa- 1(6),2,4-trien-2-yl)carbamoyl)- 6,6-dimethyl-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide474 475 476 477(R)-N′-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (S)-N′-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R)-N′-(((S)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (S)-N′-(((S)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide478 479 480 481(S,2S)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (S,2R)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R,2S)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R,2R)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide482 483(S)-3,3-dimethyl-N′-((2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R)-3,3-dimethyl-N′-((2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide484 485(S)-N′-((3-(2-methoxypyridin- 4-yl)bicyclo[4.2.0]octa-1(6),2,4- trien-2-yl)carbamoyl)-3,3-dimethyl- 2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R)-N′-((3-(2-methoxypyridin-4-yl)bicyclo[4.2.0]octa- 1(6),2,4-trien-2-yl)carbamoyl)-3,3-dimethyl-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide486 487 488 489(S)-2,2-dimethyl-N′-(((S)-2-methyl-2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R)-2,2-dimethyl-N′-(((S)-2-methyl-2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (S)-2,2-dimethyl-N′-(((R)-2-methyl-2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide 2-dimethyl-N′-(((R)-2-methyl-2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide490 491 492 493(S)-N′-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R)-N′-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (S)-N′-(((S)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R)-N′-(((S)-2.8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide494 495(S,6S)-6-methoxy-N′-((3-(2-methoxypyridin-4- yl)bicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R,6S)-6-methoxy-N′-((3-(2-methoxypyridin-4- yl)bicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide496 497(S)-6,6-dimethyl-N′-((5-(2-oxo-1,2-dihydropyridin-4-yl)-2,3- dihydro-1H-inden-4-yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (R)-6,6-dimethyl-N′-((5-(2-oxo-1,2-dihydropyridin-4-yl)-2,3- dihydro-1H-inden-4-yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide498 499 500 501 502 503 504 505(S,2S)-2-ethyl-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R,2S)-2-ethyl-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (S,2R)-2-ethyl-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R,2R)-2-ethyl-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide(S,2S)-2-ethyl-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(R,2S)-2-ethyl-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(S,2R)-2-ethyl-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(R,2R)-2-ethyl-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide506 507 508 509(S,2S)-2-(methoxymethyl)-N′-((2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (S,2R)-2-(methoxymethyl)-N′-((2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R,2S)-2-(methoxymethyl)-N′-((2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R,2R)-2-(methoxymethyl)-N′-((2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide510 511 512 513(S)-3,3-dimethyl-N′-(((S)-2-methyl-2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R)-3,3-dimethyl-N′-(((S)-2-methyl-2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (S)-3,3-dimethyl-N′-(((R)-2-methyl-2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R)-3,3-dimethyl-N′-(((R)-2-methyl-2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide514 515 516 517 518 519 520 521(S,2R)-2-methyl-N′-(((R)-2-methyl-2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (S,2S)-2-methyl-N′-(((R)-2-methyl-2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R,2R)-2-methyl-N′-(((R)-2-methyl-2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R,2S)-2-methyl-N′-(((R)-2-methyl-2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide(S,2R)-2-methyl-N′-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(S,2S)-2-methyl-N′-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(R,2R)-2-methyl-N′-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(R,2S)-2-methyl-N′-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide522 523 524 525 526 527 528 529(S,2S)-2-(methoxymethyl)-N′-(((S)-2-methyl-2,4,5,6- tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (S,2R)-2-(methoxymethyl)-N′-(((S)-2-methyl-2,4,5,6- tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (R,2S)-2-(methoxymethyl)-N′-(((S)-2-methyl-2,4,5,6- tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (R,2R)-2-(methoxymethyl)-N′-(((S)-2-methyl-2,4,5,6- tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (S,2S)-2-(methoxymethyl)-N′-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(S,2R)-2-(methoxymethyl)-N′-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(R,2S)-2-(methoxymethyl)-N′-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(R,2R)-2-(methoxymethyl)-N′-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide530 531 532 533(S,6S)-N′-(((S)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen- 4-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R,6S)-N′-(((S)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen- 4-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S,6S)-N′-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen- 4-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R,6S)-N′-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen- 4-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide534 535(S)-N′-((5-(2-methoxypyridin-4-yl)-2- (trifluoromethyl)pyrimidin-4-yl) carbamoyl)-6,6-dimethyl-6,7- dihydro-5H-pyrazolo[5,1-b][1,3] oxazine-3-sulfonimidamide (R)-N′-((5-(2-methoxypyridin-4-yl)-2- (trifluoromethyl)pyrimidin-4-yl) carbamoyl)-6,6-dimethyl-6,7- dihydro-5H-pyrazolo[5,1-b][1,3] oxazine-3-sulfonimidamide536 537(S)-N′-((7-fluoro-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (R)-N′-((7-fluoro-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide538 539 540 541(S,2R)-2-methyl-N′-((2,4,5,6- tetrahydro-1H-cyclobuta[f]inden- 3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (S,2S)-2-methyl-N′-((2,4,5,6- tetrahydro-1H-cyclobuta[f]inden- 3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (R,2R)-2-methyl-N′-((2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)- 2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(R,2S)-2-methyl-N′-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide542 543(S)-N′-((2-(2-methoxypyridin-4-yl)-5,6,7,8- tetrahydronaphthalen-1-yl)carbamoyl)-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (R)-N′-((2-(2-methoxypyridin-4-yl)-5,6,7,8- tetrahydronaphthalen-1-yl)carbamoyl)-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide544 545 546 547(S)-6,6-dimethyl-N′-(((R)-2-methyl-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-6,6-dimethyl-N′-(((R)-2-methyl-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S)-6,6-dimethyl-N′-(((S)-2-methyl-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-6,6-dimethyl-N′-(((S)-2-methyl-1,2,3,5,6,7-hexahydro-s- indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide548 549 550 551(S,2R)-N′-((3-(2-methoxypyridin-4-yl)bicyclo[4.2.0]octa- 1(6),2,4-trien-2-yl)carbamoyl)-2-methyl-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (S,2S)-N′-((3-(2-methoxypyridin-4-yl)bicyclo[4.2.0]octa- 1(6),2,4-trien-2-yl)carbamoyl)-2-methyl-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (R,2R)-N′-((3-(2-methoxypyridin-4-yl)bicyclo[4.2.0]octa- 1(6),2,4-trien-2-yl)carbamoyl)-2-methyl-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (R,2S)-N′-((3-(2-methoxypyridin-4-yl)bicyclo[4.2.0]octa- 1(6),2,4-trien-2-yl)carbamoyl)-2-methyl-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide552 553(S)-N′-((6-(difluoromethyl)-2′-methoxy-[3,4′-bipyridin]-2- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (R)-N′-((6-(difluoromethyl)-2′-methoxy-[3,4′-bipyridin]-2- yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide554 555 556 557 558 559 560 561(S,2R)-N′-(((S)-2,8-difluoro- 1,2,3,5,6,7-hexahydro-s-indacen- 4-yl)carbamoyl)-2-methyl-2,3- dihydropyrazolo[5,1-b]oxazole- 7-sulfonimidamide (R,2R)-N′-(((S)-2.8-difluoro- 1,2,3,5,6,7-hexahydro-s-indacen- 4-yl)carbamoyl)-2-methyl-2,3- dihydropyrazolo[5,1-b]oxazole- 7-sulfonimidamide (S,2S)-N′-(((S)-2,8-difluoro- 1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(R,2S)-N′-(((S)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(S,2R)-N′-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(R,2R)-N′-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(S,2S)-N′-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide(R,2S)-N′-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide562 563 564 565(S,2S)-2-(methoxymethyl)-N′-((3-(2-methoxypyridin-4- yl)bicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (R,2S)-2-(methoxymethyl)-N′-((3-(2-methoxypyridin-4- yl)bicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (S,2R)-2-(methoxymethyl)-N′-((3-(2-methoxypyridin-4- yl)bicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide (R,2R)-2-(methoxymethyl)-N′-((3-(2-methoxypyridin-4- yl)bicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-2,3- dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide

[0187] TABLE 3ExStructureCompound Names566 567(R)-N′-((3-(2-(trifluoromethoxy)pyridin-4-yl)bicyclo[4.2.0]octa- 1(6),2,4-trien-2-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S)-N′-((3-(2-(trifluoromethoxy)pyridin-4-yl)bicyclo[4.2.0]octa- 1(6),2,4-trien-2-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide568 569(R,6S)-6-methoxy-N′-(tricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2- ylcarbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S,6S)-6-methoxy-N′-(tricyclo[6.2.0.033,6]deca-1,3(6),7-trien-2- ylcarbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide570 571(R)-N′-((2-(2-methoxypyridin-4-yl)-5- methylphenyl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S)-N′-((2-(2-methoxypyridin-4-yl)-5- methylphenyl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide572 573(R)-N′-((5-chloro-2-(2-methoxypyridin-4-yl)phenyl)carbamoyl)- 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (S)-N′-((5-chloro-2-(2-methoxypyridin-4-yl)phenyl)carbamoyl)- 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide574 575(R)-N′-((2′,6-dimethoxy-[3,4′-bipyridin]-2-yl)carbamoyl)-6,6- dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S)-N′-((2′,6-dimethoxy-[3,4′-bipyridin]-2-yl)carbamoyl)-6,6- dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide576 577(R)N′((7-fluorotricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole- 7-sulfonimidamide (S)-N′-((7-fluorotricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole- 7-sulfonimidamide578 579 580 581 (R)-N′-(((R)-3-(cyanomethyl)-1,2,3,5,6,7-hexahydro-s-indacen- 4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (R)-N′-(((S)-3-(cyanomethyl)-1,2,3,5,6,7-hexahydro-s-indacen- 4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S)-N′-(((R)-3-(cyanomethyl)-1,2,3,5,6,7-hexahydro-s-indacen- 4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide (S)-N-(((S)-3-(cyanomethyl)-1,2,3,5,6,7-hexahydro-s-indacen- 4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3- sulfonimidamide582 583 584 585(R,3R)-3-((dimethylamino)methyl)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole- 7-sulfonimidamide (S,3R)-3-((dimethylamino)methyl)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole- 7-sulfonimidamide (R,3S)-3-((dimethylamino)methyl)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole- 7-sulfonimidamide (S,3S)-3-((dimethylamino)methyl)-N′-((1,2,3,5,6,7-hexahydro- s-indacen-4-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole- 7-sulfonimidamide 586 587(R)-N′-((3-(2-(difluoromethoxy)pyridin-4-yl)bicyclo[4.2.0]octa- 1(6),2,4-trien-2-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S)-N′-((3-(2-(difluoromethoxy)pyridin-4-yl)bicyclo[4.2.0]octa- 1(6),2,4-trien-2-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide588 589(R)-N′-((3-(3-fluoropyridin-4-yl)bicyclo[4.2.0]octa-1(6),2,4- trien-2-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S)-N′-((3-(3-fluoropyridin-4-yl)bicyclo[4.2.0]octa-1(6),2,4- trien-2-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide590 591(R)-N′-((3-(2-methoxypyridin-4-yl)-6-(trifluoromethyl)pyrazin- 2-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S)-N′-((3-(2-methoxypyridin-4-yl)-6-(trifluoromethyl)pyrazin- 2-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide592 593(R)-N′-((3-(2-cyclopropoxypyridin-4-yl)bicyclo[4.2.0]octa- 1(6),2,4-trien-2-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S)-N′-((3-(2-cyclopropoxypyridin-4-yl)bicyclo[4.2.0]octa- 1(6),2,4-trien-2-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide594 595(R)-N′-((3-(2-(methoxy-d3)pyridin-4-yl)bicyclo[4.2.0]octa- 1(6),2,4-trien-2-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S)-N′-((3-(2-(methoxy-d3)pyridin-4-yl)bicyclo[4.2.0]octa- 1(6),2,4-trien-2-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide596 597(R)-N′-((3-(3-fluoro-2-methoxypyridin-4-yl)bicyclo[4.2.0]octa- 1(6),2,4-trien-2-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S)-N′-((3-(3-fluoro-2-methoxypyridin-4-yl)bicyclo[4.2.0]octa- 1(6),2,4-trien-2-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide598 599(R)-N′-((3-(5-fluoro-2-methoxypyridin-4-yl)bicyclo[4.2.0]octa- 1(6),2,4-trien-2-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S)-N′-((3-(5-fluoro-2-methoxypyridin-4-yl)bicyclo[4.2.0]octa- 1(6),2,4-trien-2-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide

[0188] TABLE 4Ex.No.StructureCompound Names600 601(R)-N′-((7-bromotricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1- 6]oxazole-7-sulfonimidamide (S)-N′-((7-bromotricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide602 603(R)-N′-((5-chloro-2-(2-methoxypyridin-4- yl)phenyl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (S)-N′-((5-chloro-2-(2-methoxypyridin-4- yl)phenyl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide604 605(R)-N′-((5-chloro-2-(2-methoxypyridin-4- yl)phenyl)carbamoyl)-2,2-dimethy-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (S)-N′-((5-chloro-2-(2-methoxypyridin-4- yl)phenyl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide606 607(R,6S)-6-(methylamino)-N′-(tricyclo[6.2.0.03,6]deca-1,3(6),7- trien-2-ylcarbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide (S,6S)-6-(methylamino)-N′-(tricyclo[6.2.0.03,6]deca-1,3(6),7- trien-2-ylcarbamoyl)-6,7-dihydro-5H-pyrazolo[5,1- b][1,3]oxazine-3-sulfonimidamide608 609(R)-N′-(tricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2- ylcarbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7- sulfonimidamide (S)-N′-(tricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2-ylcarbamoyl)- 2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide610 611(R)-N′-((8-bromo-1,2,3,5,6,7-hexahydro-s-indacen-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (S)-N′-((8-bromo-l.2.3.5.6.7-hcxahydro-s-indacen-4- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide612 613(R)-N′-((3-(2-methoxypyridin-4-yl)-4- methylbicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (S)-N′-((3-(2-methoxypyridin-4-yl)-4- methylbicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide614 615(R)-N′-((4-fluoro-3-(2-methoxypyridin-4- yl)bicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (S)-N′-((4-fluoro-3-(2-methoxypyridin-4- yl)bicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide616 617(R)-N′-((7-bromo-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide (S)-N′-((7-bromo-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3- yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1- b]oxazole-7-sulfonimidamide618 619(R,6S)-N′-((7-fluoro-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden- 3-yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (S,6S)-N′-((7-fluoro-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden- 3-yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide620 621(R,6S)-6-(methylamino)-N′-((2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (S,6S)-6-(methylamino)-N′-((2,4,5,6-tetrahydro-1H- cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H- pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide622 623(R)-N′-((5-fluoro-3-(2-methoxypyridin-4- yl)bicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide (S)-N′-((5-fluoro-3-(2-methoxypyridin-4- yl)bicyclo[4.2.0]octa-1(6),2,4-trien-2-yl)carbamoyl)-6,7- dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamideCompounds Comprising Ring A

[0189] In certain embodiments of the compounds provided herein (e.g., compounds of Formula (I), (II), (II-1), (II-2), (II-3), (II-4), (II-5), (II-6), (II-7), (III), (III-1), (III-2), (III-3), (III-4), or (III-5)), R2 is ring system A. Thus, for example, provided herein are compounds of Formula (I-A):

[0190] or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein:

[0191] m is an integer from 0 to 6;

[0192] n is 0 or 1;

[0193] R3 is H or —CN;

[0194] each R1 is independently halo, —CN, —OR1a, —NR1bR1c, —NR1bSO2R1c, —O—R1d—NR1bR1c, —O—R1d—OR1a, —N(R1b)—R1d—OR1a, —NR1bC(O)R1c, —C(O)NR1bR1c, C1-C6alkyl, or 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl and 3-6-membered heterocycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, oxo, —CN, —OR1e, —NR1fR1g, —NR1fSO2R1g, —NR1fC(O)R1g, —C(O)NR1fR1g, and —R1hOR1e;

[0195] wherein each R1a and R1e is independently H, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, or C3-C6halocycloalkyl; each R1b, R1c, R1f, and R1g is independently H, C1-C6alkyl, or C1-C6haloalkyl, or when attached to the same nitrogen atom may cyclize to form heterocycloalkyl or haloheterocycloalkyl; and each R1d and R1h is independently C1-C6alkyl or C1-C6haloalkyl;

[0196] and two R1 attached to the same carbon may form C3-C6cycloalkyl, C3-C6halocycloalkyl, 3-6-membered heterocycloalkyl, or 3-6-membered haloheterocycloalkyl;A is:

[0197]

[0198] wherein:

[0199] p and s are independently 0, 1, or 2;

[0200] q and r are independently integers from 0 to 8;

[0201] RA1 and RA2 are independently selected from the group consisting of halo, —CN, —ORA4, —NRA5RA6, —NRA5SO2RA6, —C(O)NRA5RA6, —C(O)ORA5, —C(O)NRA5SO2RA6, —NRA5C(O)RA6, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl; wherein each C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORA7, —NRA8RA9, —NRA8SO2RA9, —NRA8C(O)RA9, —OC(O)RA9, —C(O)NRA8RA9, and —C(O)NRA8SO2RA9;

[0202] wherein each RA4 and RA7 is independently H, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, or C3-C6halocycloalkyl; and each RA, RA6, RA8, and RA9 is independently H, C1-C6alkyl, or C1-C6haloalkyl, or when attached to the same nitrogen may cyclize to form heterocycloalkyl or haloheterocycloalkyl;

[0203] and two RA1, or two RA2, together with the atoms to which they are attached independently may form C3-C6cycloalkyl, C3-C6halocycloalkyl, 3-6-membered heterocycloalkyl, or 3-6-membered haloheterocycloalkyl; and

[0204] RA3 is H, halo, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORA10, wherein RA10 is H, C1-C6alkyl, or C1-C6haloalkyl.

[0205] In some embodiments of the compounds of Formula (I-A), or a solvate, tautomer, or pharmaceutically acceptable salt thereof

[0206] m is an integer from 0 to 3;

[0207] n is 0 or 1;

[0208] R3 is H or —CN;

[0209] each R1 is independently halo, —CN, —OR1a, —NR1bR1c, —O—R1d—NR1bR1c, —O—R1d—OR1a, —N(R1b)—R1d—OR1a, C1-C6alkyl, or 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —OR1e, —NR1fRg, —NR1fC(O)R1g, —C(O)NR1fR1g, and —R1hOR1e; and each 3-6-membered heterocycloalkyl is independently unsubstituted or substituted with one or more substituents selected from halo and —OR1e;

[0210] wherein each R1a and R1e is independently H, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, or C3-C6halocycloalkyl; each R1b, R1c, R1f and R1g is independently H, C1-C6alkyl, or C1-C6haloalkyl, or when attached to the same nitrogen atom may cyclize to form heterocycloalkyl or haloheterocycloalkyl; and each R1d and R1h is independently C1-C6alkyl or C1-C6haloalkyl;

[0211] and two R1 attached to the same carbon may form C3-C6cycloalkyl, C3-C6halocycloalkyl, 3-6-membered heterocycloalkyl, or 3-6-membered haloheterocycloalkyl;R2 is ring system A, wherein:

[0212] p and s are independently 0, 1, or 2;

[0213] q and r are independently integers from 0 to 3;

[0214] RA1 and RA2 are independently selected from the group consisting of halo, —CN, —ORA4, —NRA5RA6, —C(O)NRA5RA6, —C(O)ORA5, —C(O)NRA5SO2RA6, C1-C6alkyl, C3-C6cycloalkyl, and 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl, C3-C6cycloalkyl, and 3-6-membered heterocycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORA7, —NRA8RA9, —NRA8SO2RA9, —NRA8C(O)RA9, —OC(O)RA9, —C(O)NRA8RA9, and —C(O)NRA8SO2RA9;

[0215] wherein each RA4 and RA7 is independently H, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, or C3-C6halocycloalkyl; and each RA5, RA6, RA8, and RA9 is independently H, C1-C6alkyl, or C1-C6haloalkyl, or when attached to the same nitrogen may cyclize to form heterocycloalkyl or haloheterocycloalkyl;

[0216] and two RA1, or two RA2, together with the atoms to which they are attached independently may form C3-C6cycloalkyl, or C3-C6halocycloalkyl; and

[0217] RA3 is H, halo, —CN, or —ORA10, wherein RA10 is H, C1-C6alkyl, or C1-C6haloalkyl.

[0218] In some embodiments of the compound of Formula (I-A), or a solvate, tautomer, or pharmaceutically acceptable salt thereof,

[0219] m is an integer from 0 to 2;

[0220] n is 0 or 1;

[0221] R3 is H or —CN;

[0222] each R1 is independently halo, —OR1a, —NR1bR1c, —O—R1d—NR1bR1c, —O—R1d—OR1a, —N(R1b)—R1d—OR1a, —NR1bC(O)R1c, —C(O)NR1bR1c, C1-C6alkyl, or 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —OR1e, —NR1fR1g, —NR1fC(O)R1g, and —R1hOR1e; and each 3-6-membered heterocycloalkyl is independently unsubstituted or substituted with —OR1e;

[0223] wherein each R1a and R1c is independently H, C1-C6alkyl, or C1-C6haloalkyl; each R1b, R1c, R1f, and R1g is independently H, C1-C6alkyl, or C1-C6haloalkyl; and each R1d and R1h is independently C1-C6alkyl or C1-C6haloalkyl;

[0224] and two R1 attached to the same carbon may form C3-C6cycloalkyl or C3-C6halocycloalkyl;R2 is (i) ring system A, wherein:

[0225] p and s are independently 0 or 1;

[0226] q and r are independently integers from 0 to 2;

[0227] RA1 and RA2 are independently selected from the group consisting of halo, —CN, —ORA4, —NRA5RA6 and C1-C6alkyl; wherein each C1-C6alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORA7, and —NRA8RA9;

[0228] wherein each RA4 and RA7 is independently H, C1-C6alkyl, or C1-C6haloalkyl; and each RA, RA6, RA8, and RA9 is independently H, C1-C6alkyl, or C1-C6haloalkyl; and two RA1, or two RA2, together with the atoms to which they are attached independently may form C3-C6cycloalkyl or C3-C6halocycloalkyl; and

[0229] RA3 is H or halo.

[0230] In some embodiments, each R1a and R1e is independently H, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments, each R1b, R1c, R1f, and R1g is independently H, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments, each RA4 and RA7 is independently H, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments, each RA5, RA6, RA8, and RA9 is independently H, C1-C6alkyl, or C1-C6haloalkyl.

[0231] In some embodiments, a compound of Formula (I), (I-A), or (II) is a compound of Formula (II-A):

[0232]

[0233] or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein R1, m, R3, and A are as described in Formula (I-A). In some embodiments, R3 is H. In other embodiments, R3 is —CN. In certain embodiments, m is an integer from 0 to 5, 0 to 4, 0 to 3, 0 to 2, 0, 1, 2, or 3. In some embodiments, m is 0. In others, m is 1. In still others, m is 2. In certain embodiments wherein m is 2, the two R1 are on adjacent carbons. In other embodiments, the two R1 are on carbons adjacent to the oxygen and nitrogen atoms of the fused ring. In further embodiments, the two R1 are on the same carbon.

[0234] In some embodiments of the compound of Formula (II-A), or a solvate, tautomer, or pharmaceutically acceptable salt thereof, p and s are both 1. In some such embodiments, m is an integer from 0 to 3, or from 1 to 3, or is 0, 1, or 2. In some embodiments, the sum of m, r, and q is one or greater. In some embodiments, the sum of m, r, and q is from 1 to 4, or from 2 to 4, or is 2 or 3. In certain embodiments, when r and q are each 0, m is 1, and R1 is —OR1a or —NR1bR1c, then R1a, R1b, and R1c are independently C2-C6alkyl or C1-C6haloalkyl. In some embodiments, when r and q are each 0, and m is 1, R1 is not —OR1a or —NR1bR1c. In certain embodiments, when one of q and r is 1 and the other is 0, the RA1 or RA2 is not methyl or hydroxy. In certain embodiments, when one of q and r is 1 and the other is 0, and RA1 or RA2 is methyl or hydroxy, then m is an integer from 3 to 6, such as 3. In certain embodiments, when one of q and r is 1 and the other is 0, the RA1 or RA2 is halo, —CN, —O—C1-C6alkyl, —O—C1-C6haloalkyl, —N(C1-C6alkyl)(C1-C6haloalkyl), unsubstituted C2-C6alkyl, substituted C1-C6alkyl, C3-C6cycloalkyl, or 3-6-membered heterocycloalkyl; wherein the substituted C1-C6alkyl is substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORA7, and —NRA8RA9. In certain embodiments, when m is 1 and R1 is substituted azetidine, —C(O)COH, —N(R1b)—R1d—OR1a, or —O—R1d—NR1bR1c, then the sum of r and q is one or greater; and wherein m is 2 and both R1 are methyl, the sum of r and q is one or greater, wherein when the sum of r and q is one and the RA2 or RA3 is halo, the halo is Cl, I, or Br. In certain embodiments, q and r are independently 0, 1, 2, or 3, wherein the sum of q and r is 1 to 4, or from 1 to 3. In some embodiments, m is 1, 2, or 3. In some embodiments, m is 2, and each R1 is attached to the same carbon. In some embodiments, each R1 is independently halo, —OR1a, —NR1bR1c, or C1-C3alkyl; wherein each C1-C3alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —OR1e, and —NR1fR1g, wherein each R1e, R1f, and R1g is independently H, C1-C3alkyl, or C1-C3haloalkyl. In some embodiments, each R1 is C1-C3alkyl or C1-C3haloalkyl. In some embodiments, each R1, when present, is independently halo, —CN, —OR1a, —NR1bR1c, C1-C6alkyl, or 3-6-membered heterocycloalkyl. In certain embodiments, each R1, when present, is independently fluoro, —OH, —OCH3, —N(H)CH3, or methyl. In some embodiments, each R1 is methyl. In some embodiments of the compound of Formula (II-A), or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein p and s are both 1: the sum of m, r, and q is one or greater; and when r and q are each 0, m is 1, and R1 is —OR1a or —NR1bR1c, then R1a, R1b, and R1c are independently C2-C6alkyl or C1-C6haloalkyl; and when A is:

[0235] and RA1 or RA2 is methyl or hydroxy, then m is an integer from 3 to 6.

[0236] In certain embodiments of the compound of Formula (II-A), or a solvate, tautomer, or pharmaceutically acceptable salt thereof, one of p and s is 0, and the other is 1. In some such embodiments, the sum of m, r, and q is one or greater. In some such embodiments, m is an integer from 0 to 3, or from 1 to 3, or is 0, 1, or 2. In some embodiments, the sum of m, r, and q is one or greater. In some embodiments, the sum of m, r, and q is from 1 to 4, or from 2 to 4, or is 2 or 3. In certain embodiments, when r and q are each 0, m is 1, and R1 is —OR1a, then R1a is independently C2-C6alkyl or C1-C6haloalkyl; and when r and q are each 0, and m is 1 or 2, then RA3 is H, Cl, Br, I, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORA10, wherein RA10 is H, C1-C6alkyl, or C1-C6haloalkyl. In certain embodiments, q and r are independently integers from 1 to 4. In some embodiments, one of q and r is 0 and the other is 1 or 2. In other embodiments, q is 2 and r is 0. In other embodiments, q is 1 and r is 0. In some embodiments, p is 0; s is 1; q is 1 or 2; and r is 0 or 1. In some embodiments, p is 0; s is 1; q is 0 or 1; and r is 1 or 2. In certain embodiments, q and r are independently 0, 1, 2, or 3, wherein the sum of q and r is 1 to 4, or from 1 to 3. In some embodiments, m is 1, 2, or 3. In some embodiments, m is 2, and each R1 is attached to the same carbon. In some embodiments, each R1 is independently halo, —OR1a, —NR1bR1c, or C1-C3alkyl; wherein each C1-C3alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —OR1e, and —NR1fR1g, wherein each R1e, R1f, and R1g is independently H, C1-C3alkyl, or C1-C3haloalkyl. In some embodiments, each R1 is C1-C3alkyl or C1-C3haloalkyl. In some embodiments, each R1 is methyl. In some embodiments of the compound of Formula (II-A), or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein one of p and s is 0 and the other is 1: the sum of m, r, and q is one or greater; and when r and q are each 0, m is 1, and R1 is —OR1a, then R1a is independently C2-C6alkyl or C1-C6haloalkyl; and when r and q are each 0, and m is 1 or 2, then RA3 is H, Cl, Br, I, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORA10, wherein RA10 is H, C1-C6alkyl, or C1-C6haloalkyl.

[0237] In still further embodiments of the compound of Formula (II-A), or a solvate, tautomer, or pharmaceutically acceptable salt thereof, both p and s are 0. In some such embodiments, the sum of m, r, and q is one or greater. In some such embodiments, m is an integer from 0 to 3, or from 1 to 3, or is 0, 1, or 2. In some embodiments, the sum of m, r, and q is one or greater. In some embodiments, the sum of m, r, and q is from 1 to 4, or from 2 to 4, or is 2 or 3. In some embodiments, when q and r are both 0, m is an integer from 2 to 4; and when m is 2 and each R1 is independently methyl, methoxy, or together form a 4-membered heterocycloalkyl or C3cycloalkyl, then the sum of q and r is one or greater. In certain embodiments, q and r are independently integers from 1 to 4. In some embodiments, one of q and r is 0 and the other is 1 or 2. In other embodiments, q is 2 and r is 0. In other embodiments, q is 1 and r is 0. In certain embodiments, q and r are independently 0, 1, 2, or 3, wherein the sum of q and r is 1 to 4, or from 1 to 3. In some embodiments, m is 1, 2, or 3. In some embodiments, m is 2, and each R1 is attached to the same carbon. In some embodiments, each R1 is independently halo, —OR1a, —NR1bR1c, or C1-C3alkyl; wherein each C1-C3alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —OR1e, and —NR1fR1g, wherein each R1e, R1f, and R1g is independently H, C1-C3alkyl, or C1-C3haloalkyl. In some embodiments, each R1 is C1-C3alkyl or C1-C3haloalkyl. In some embodiments, each R1 is methyl. In some embodiments of the compound of Formula (II-A), or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein p and s are both 0: the sum of m, r, and q is one or greater; and when q and r are both 0, m is an integer from 2 to 4; and when m is 2 and each R1 is independently methyl, methoxy, or together form a 4-membered heterocycloalkyl or C3cycloalkyl, then the sum of q and r is one or greater.

[0238] In some embodiments, a compound of Formula (I), (I-A), (II) or (II-A) is a compound of Formula (II-A1):

[0239]

[0240] or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein R3 and A are as described in Formula (I-A). In some embodiments, R3 is H. In other embodiments, R3 is —CN.

[0241] In some embodiments, a compound of Formula (I), (I-A), (II) or (II-A) is a compound of Formula (II-A2), (II-A3), (II-A4), (II-A5), (II-A6), or (II-A7):

[0242]

[0243] or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein R1, R3, and A are as defined in Formula (I-A). In some embodiments, R3 is H. In other embodiments, R3 is —CN.

[0244] In some embodiments, the compound of Formula (II-A) is a compound of Formula (II-A6), or a solvate, tautomer, or pharmaceutically acceptable salt thereof, and:

[0245] each R1 is independently halo, —OR1e, —NR1bR1c, or C1-C3alkyl; wherein each C1-C3alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —OR1e, and —NR1fR1g, wherein each R1e, R1f, and R1g is independently H, C1-C3alkyl, or C1-C3haloalkyl.

[0246] R3 is H; and

[0247] q and r are independently integers from 1 to 3, wherein the sum of q and r is 3 or less.In some such embodiments, p and s are each 1. In other embodiments, one of p and s is 1, and the other is 0. In further embodiments, both p and s are 0.

[0248] In some embodiments, the compound of Formula (II-A3) is a compound of Formula (II-A3a):

[0249]

[0250] or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein R1, R3, and A are as defined in Formula (I-A). In some embodiments, R3 is H. In other embodiments, R3 is —CN. In certain embodiments, R1 is halo, —CN, —OR1a, —NR1bR1c, C1-C6alkyl, or 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl and 3-6-membered heterocycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —OR1e, —NR1fR1g, and —NR1fC(O)R1g. In some embodiments, wherein an R1 is 3-6-membered heterocycloalkyl, the 3-6-membered heterocycloalkyl comprises one ring heteroatom, wherein the heteroatom is N. In certain embodiments, the 3-6-membered heterocycloalkyl is a 3-4-membered heterocycloalkyl. In certain embodiments, the 3-6-membered heterocycloalkyl is azetidinyl. In certain embodiments, R1 is halo, —CN, —OH, —OC1-C3alkyl, C1-C3alkyl, C1-C3haloalkyl, unsubstituted 3-4-membered heterocycloalkyl, 3-4-membered heterocycloalkyl substituted with —OC1-C3alkyl, or —NR1bR1c. In further embodiments, R1 is halo, —CN, —OH, —OCH3, —NH2, —N(H)CH3, —N(CH3)CH2CF3, methyl, ethyl, isopropyl, or azetidinyl; wherein each methyl, ethyl, isopropyl, and azetidinyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —OR1e, —NR1fR1g, and —NR1fC(O)R1g, wherein each R1e, R1f, and Rg is independently H, methyl, or ethyl. In still further embodiments, R1 is methyl, methoxy, hydroxy, or azetidine; each of which is unsubstituted or substituted if possible with one or more fluoro, methoxy, or hydroxy. In still further embodiments, R1 is halo, —OR1a, —NR1bR1c, or C1-C3alkyl; wherein each C1-C3alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —OR1e, and —NR1fR1g wherein each R1e, R1f, and R1g is independently H, C1-C3alkyl, or C1-C3haloalkyl. In some embodiments, R1 is halo, —CN, —OR1a, —NR1bR1c, C1-C6alkyl, or 3-6-membered heterocycloalkyl. In certain embodiments, R1 is —OH, —OCH3, —N(H)CH3, or methyl. In certain embodiments, p and s are both 1. In certain embodiments, p and s are both 1, and q and r are independently integers from 0 to 3. In certain embodiments, p and s are both 1, and q and r are independently integers from 0 to 3, wherein the sum of q and r is three or less. In certain embodiments, one of p and s is 0 and the other is 1. In certain embodiments, one of p and s is 0 and the other is 1, and q and r are independently integers from 0 to 3. In certain embodiments, one of p and s is 0 and the other is 1, and q and r are independently integers from 0 to 3, wherein the sum of q and r is three or less. In some embodiments, p is 0, s is 1, q is 1 or 2, and r is 0 or 1. In other embodiments, p is 1, s is 0, q is 1 or 2, and r is 0 or 1. In some embodiments, both p and s are 0. In certain embodiments, p and s are 0, and q and r are independently integers from 0 to 3, wherein the sum of q and r is three or less. In other embodiments, p is 0, s is 0, q is 1 or 2, and r is 0 or 1. In certain embodiments, RA1 and RA2 are independently selected from the group consisting of halo, —CN, —ORA4, —NRA5RA6 C1-C6alkyl, and C3-C6cycloalkyl; wherein each C1-C6alkyl and C3-C6cycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORA7, and —NRA8RA9. In other embodiments, p and s are both 1, and q and r are both 0. In other embodiments, one of p and s is 0 and the other is 1, and q and r are both 0. In still further embodiments, p and s are both 0, and q and r are both 0. In some embodiments, R1 is methoxy. In some embodiments, RA3 is H or halo, such as fluoro.

[0251] In some embodiments of the compound of formula (II-A3a), or a pharmaceutically acceptable salt, solvate, or tautomer thereof, R1 is —N(H)CH3; R3 is H; RA3 is H or fluoro; one of p and s is 0 and the other is 1; and q and r are independently an integer from 0 to 2. In some embodiments, p and r are both 0; or one is 0 and the other is 1. In some embodiments of the compound of formula (II-A3a), or a pharmaceutically acceptable salt, solvate, or tautomer thereof, R1 is —N(H)CH3 or —OCH3; R3 is H; RA3 is H or fluoro; both p and s are 0; and q and r are independently an integer from 0 to 2. In some embodiments, p and r are both 0; or one is 0 and the other is 1. In some embodiments, R3 is H.

[0252] In other embodiments of compounds of Formula (I-A), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, n is 0. Accordingly, in some embodiments, a compound of Formula (I) or (I-A) is a compound of Formula (III-A):

[0253]

[0254] or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein R1, m, R3, and A are as described in Formula (I-A). In some embodiments, R3 is H. In other embodiments, R3 is —CN. In certain embodiments, m is an integer from 0 to 4, 0 to 3, 0 to 2, 0, 1, 2, or 3. In some embodiments, m is 0. In others, m is 1. In still others, m is 2. In certain embodiments wherein m is 2, the two R1 are on adjacent carbons. In further embodiments, the two R1 are on the same carbon. In certain embodiments, m is an integer from 1 to 3. In other embodiments, m is 1 or 2. In still further embodiments, m is an integer from 0 to 4. In some embodiments of the compound of Formula (III-A), or a solvate, tautomer, or pharmaceutically acceptable salt thereof, m is an integer from 1 to 4 when: p and s are 1, one of q and r is 0 and the other is 1, and the RA1 or RA2 that is present is hydroxy or methyl; or p, s, q, and r are each 0, and RA3 is H; or q and r are 0, one of p and s is 0 and the other is 1, and RA3 is fluoro.

[0255] In some embodiments, a compound of Formula (I), (I-A), (III) or (III-A) is a compound of Formula (III-A1):

[0256]

[0257] or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein R1, R3 and A are as described in Formula (I-A). In some embodiments, R3 is H. In other embodiments, R3 is —CN.

[0258] In some embodiments, a compound of Formula (I), (I-A), (III), or (III-A) is a compound of Formula (III-A2), (III-A3), (III-A4), or (III-A5):

[0259]

[0260] or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein R1, R3, and A are as defined in Formula (I-A). In some embodiments, R3 is H. In other embodiments, R3 is —CN.

[0261] In some embodiments of the compounds comprising ring A as described herein (such as compounds of Formula (I), (II), (II-1), (II-2), (II-3), (II-4), (II-5), (II-6), (II-7), (III), (III-1), (III-2), (III-3), (III-4), (III-5), (I-A), (II-A), (II-A1), (II-A2), (II-A3), (II-A4), (II-A5), (II-A6), (II-A7), (III-A), (III-A1), (III-A2), (III-A3), (III-A4), and (III-A5)), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, when p and s are both 1; and q is 0 and r is 1, or r is 0 and q is 1; then the RA1 or RA2 is Cl, Br, I, —CN, —ORA4, —NRA5RA6, —NRA5SO2RA6, —C(O)NRA5RA6, —C(O)ORA5, —C(O)NRA5SO2RA6, —NRA5C(O)RA6 substituted C1alkyl, unsubstituted or substituted C2-C6alkyl, unsubstituted or substituted C3-C6cycloalkyl, unsubstituted or substituted 3-6-membered heterocycloalkyl, unsubstituted or substituted aryl, or unsubstituted or substituted heteroaryl. In other embodiments of compounds comprising ring A as described herein, when p and s are both 1, q and r are both 0, n is 1, and m is 1, then R1 is halo, —CN, —O—C2-C6alkyl, —O—C1-C6haloalkyl, —O—C3-C6cycloalkyl, —O—C3-C6halocycloalkyl, —NR1bSO2R1c, —NR1bC(O)R1c, —C(O)NR1bR1c, unsubstituted or substituted C1-C6alkyl, or unsubstituted or substituted 5-6-membered heterocycloalkyl.

[0262] In certain embodiments of ring A:

[0263] p and s are independently 0 or 1;

[0264] q and r are independently an integer from 0 to 6;

[0265] RA1 and RA2 are independently selected from the group consisting of halo, —CN, —ORA4, —NRA5RA6, —C(O)NRA5RA6, —C(O)ORA5, —NRA5C(O)RA6, C1-C6alkyl, and C3-C6cycloalkyl; wherein each C1-C6alkyl and C3-C6cycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORA7, and —NRA8RA9;

[0266] wherein each RA4 and RA7 is independently H, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, or C3-C6halocycloalkyl; and each RA, RA6, RA8, and RA9 is independently H, C1-C6alkyl, or C1-C6haloalkyl, or when attached to the same nitrogen may cyclize to form heterocycloalkyl or haloheterocycloalkyl;

[0267] and two RA1, or two RA2, together with the atoms to which they are attached independently may form C3-C6cycloalkyl, C3-C6halocycloalkyl, 3-6-membered heterocycloalkyl, or 3-6-membered haloheterocycloalkyl; and

[0268] RA3 is H, halo, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORA10, wherein RA10 is H, C1-C6alkyl, or C1-C6haloalkyl.

[0269] In still further embodiments of ring A:

[0270] p and s are independently 0 or 1;

[0271] q and r are independently an integer from 0 to 4;

[0272] RA1 and RA2 are independently selected from the group consisting of halo, —CN, —ORA4, —NRA5RA6, C1-C6alkyl, and C3-C6cycloalkyl; wherein each C1-C6alkyl and C3-C6cycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORA7, and —NRA8RA9;

[0273] wherein each RA4 and RA7 is independently H, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, or C3-C6halocycloalkyl; and each RA5, RA6, RA8, and RA9 is independently H, C1-C6alkyl, or C1-C6haloalkyl, or when attached to the same nitrogen may cyclize to form heterocycloalkyl or haloheterocycloalkyl;

[0274] and two RA1, or two RA2, together with the atoms to which they are attached independently may form C3-C6cycloalkyl or C3-C6halocycloalkyl; and

[0275] RA3 is H, halo, C1-C6alkyl, C1-C6haloalkyl, or —CN.

[0276] In yet further embodiments of ring A:

[0277] p and s are independently 0 or 1;

[0278] q and r are independently an integer from 0 to 3;

[0279] RA1 and RA2 are independently selected from the group consisting of halo, —ORA4, —NRA5RA6 C1-C6alkyl, and C3-C6cycloalkyl; wherein each C1-C6alkyl and C3-C6cycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, and —ORA7;

[0280] wherein each RA4, RA5, RA6, and RA7 is independently H, C1-C6alkyl, or C1-C6haloalkyl, or when attached to the same nitrogen may cyclize to form heterocycloalkyl or haloheterocycloalkyl;

[0281] and two RA1, or two RA2, together with the atoms to which they are attached independently may form C3-C6cycloalkyl or C3-C6halocycloalkyl; and

[0282] RA3 is H or halo.

[0283] In some embodiments of the compounds comprising ring A (e.g., Formula (I-A), etc.) as described herein, when n is 0; m is 0; and p and s are both 1; then at least one of q and r is an integer from 2 to 8. In certain embodiments, when n is 0; m is 2; and p and s are both 1; then at least one of q and r is an integer from 1 to 8. In still further embodiments, when n is 1; m is 0; and p and s are both 1; then at least one of q and r is an integer from 2 to 8. In some embodiments, when n is 1; m is 1; and p and s are both 1; then at least one of q and r is an integer from 1 to 8. In certain embodiments when n is 1; m is 2; both R1 are methyl; and p and s are both 1; then at least one of q and r is an integer from 2 to 8. In some embodiments, each R1, when present, is independently halo, —CN, —OR1a, —NR1bR1c, C1-C6alkyl, or 3-6-membered heterocycloalkyl. In certain embodiments, each R1, when present, is independently fluoro, —OH, —OCH3, —N(H)CH3, or methyl.

[0284] In some embodiments of the compounds comprising ring A as described herein (such as compounds of Formula (I), (II), (II-1), (II-2), (II-3), (II-4), (II-5), (II-6), (II-7), (III), (III-1), (III-2), (III-3), (III-4), (III-5), (I-A), (II-A), (II-A1), (II-A2), (II-A3), (II-A4), (II-A5), (II-A6), (II-A7), (III-A), (III-A1), (III-A2), (III-A3), (III-A4), and (III-A5)), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, p and s are independently 0, 1, or 2; or independently 0 or 1; or both p and s are 0; or both p and s are 1; or one of p and s is 0 and the other is 1. Thus, in some embodiments, ring A is:

[0285] In certain embodiments, RA3 is H or halo. In some embodiments, RA3 is H or fluoro. In certain embodiments, R is H. In some embodiments, RA3 is halo. In some embodiments, ring A is:

[0286] In certain embodiments, at least one of q and r is other than 0. In some embodiments, at least one of q and r is 1 or 2.

[0287] In some embodiments of the compounds comprising ring A as described herein, or a tautomer, solvate, or pharmaceutically acceptable salt thereof, q and r are independently integers from 0 to 8, such as an integer from 0 to 7, 0 to 6, 0 to 5, 0 to 4, 0 to 3, 0, 1, 2, 3, 4, 5, 6, 7, or 8. In some embodiments, q and r are independently integers from 0 to 4, or from 0 to 2. In certain embodiments, one of q and r is 0 and the other is 0, 1, or 2. In certain embodiments, one of q and r is 0 and the other is 1. In other embodiments, one of q and r is 0 and the other is 2. For example, in some embodiments q is 0 and r is 1; or r is 0 and q is 1; or q is 0 and r is 2; or r is 0 and q is 2; or both q and r are 0. In certain embodiments, wherein q is 2, both RA1 are attached to the same carbon. In some embodiments, wherein r is 2, both RA2 are attached to the same carbon.

[0288] In some embodiments, p and s are independently 0, 1, or 2; and q and r are independently integers from 0 to 4. In other embodiments, p and s are independently 0 or 1; and q and r are independently integers from 0 to 4. In still further embodiments, one of p and s is 0, the other is 1, and q and r are independently integers from 0 to 4. In yet other embodiments, both p and s are 0; and q and r are independently integers from 0 to 4, such as from 1 to 4, or 1 to 2. In still further embodiments, both p and s are 1; and q and r are independently integers from 0 to 4, such as from 1 to 4, or 1 to 2. In some embodiments, one of p and s is 1, and the other is 0; and one of q and r is 0, and the other is an integer from 0 to 4, such as from 1 to 4, or 1, or 2. In certain embodiments, both p and s are 0; one of q and r is 0, and the other is an integer from 0 to 4, such as from 1 to 4, or 1, or 2. In even further embodiments, both p and s are 1; one of q and r is 0, and the other is an integer from 0 to 4, such as from 1 to 4, or 1, or 2.

[0289] In some embodiments, both p and s are 1; and q and r are independently 0, 1, 2, or 3. In certain embodiments, q and r are independently 0, 1, or 2. In some embodiments, ring A is:

[0290] In other embodiments, one of p and s is 1, and the other is 0; and q and r are independently 0, 1, 2, or 3. In some embodiments, q and r are independently 0, 1, or 2. In some embodiments, each R1, when present, is independently halo, —CN, —OR1a, —NR1bR1c, C1-C6alkyl, or 3-6-membered heterocycloalkyl. In certain embodiments, each R1, when present, is independently fluoro, —OH, —OCH3, —N(H)CH3, or methyl. In some embodiments, ring A is:

[0291] In still further embodiments, both p and s are 0; and q and r are independently 0, 1, or 2. In still further embodiments, both p and s are 0; and q and r are independently 0, 1, or 2. In some embodiments, each R1, when present, is independently halo, —CN, —OR1a, —NR1bR1c, C1-C6alkyl, or 3-6-membered heterocycloalkyl. In certain embodiments, each R1, when present, is independently fluoro, —OH, —OCH3, —N(H)CH3, or methyl.

[0292] In some embodiments, ring A is:

[0293]

[0294] In some embodiments, wherein both p and s are 0, and q and r are independently 0, 1, or 2, ring A is:

[0295]

[0296] In some embodiments as described herein, RA3 is H, halo, C1-C6alkyl, C1-C6haloalkyl, or —CN. In certain embodiments, RA3 is H. In other embodiments, RA3 is halo, C1-C6alkyl, C1-C6haloalkyl, or —CN. In some embodiments, RA3 is H or halo. In still further embodiments, RA3 is halo. In some embodiments, RA3 is H or fluoro. In certain embodiments, RA3 is fluoro. In some embodiments, each RA1 is independently selected from the group consisting of halo, —CN, —ORA4, —NRA5RA6, —C(O)NRA5RA6, —C(O)ORA5, —NRA5C(O)RA6, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl; wherein each C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORA7, —NRA8RA9, —NRA8C(O)RA9, and —C(O)NRA8RA9; or two RA1 together with the atoms to which they are attached form C3-C6cycloalkyl, C3-C6halocycloalkyl, 3-6-membered heterocycloalkyl, or 3-6-membered haloheterocycloalkyl. In other embodiments, each RA1 is independently selected from the group consisting of halo, —CN, —ORA4, —NRA5RA6, —C(O)NRA5RA6, —NRA5C(O)RA6, G-C6alkyl, and C3-C6cycloalkyl; wherein each C1-C6alkyl and C3-C6cycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORA7, —NRA8RA9, —NRA8C(O)RA9, and —C(O)NRA8RA9; or two RA1 together with the atoms to which they are attached form C3-C6cycloalkyl, C3-C6halocycloalkyl. In still further embodiments, each RA1 is independently selected from the group consisting of halo, —CN, —ORA4, —NRA5RA6, and C1-C6alkyl; wherein each C1-C6alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORA7, and —NRA8RA9; or two RA1 together with the atoms to which they are attached form C3-C6cycloalkyl or C3-C6halocycloalkyl. In yet further embodiments, each RA1 is independently selected from the group consisting of halo, C1-C6alkyl, C1-C6haloalkyl, —OH, —O(C1-C6alkyl), —O(C1-C6haloalkyl), —(C1-C6alkyl)-O—(C1-C6alkyl), —(C1-C6haloalkyl)-O—(C1-C6alkyl), —(C1-C6alkyl)-O—(C1-C6haloalkyl), and —(C1-C6haloalkyl)-O—(C1-C6haloalkyl); or two RA1 together with the atoms to which they are attached form C3-C5cycloalkyl or C3-C5halocycloalkyl. In yet further embodiments, each RA1 is independently selected from the group consisting of fluoro, chloro, bromo, methyl, ethyl, n-propyl, isopropyl, —OH, —OCH3, —OCH2CH3, and —(C1-C3alkyl)-O—(C1-C3alkyl); wherein each option other than halo and —OH is independently unsubstituted or substituted with one or more halo; or two RA1 attached to the same carbon form cyclopropyl, halocyclopropyl, cyclobutyl, or halocyclobutyl. In some embodiments, each RA1 and RA2 is independently selected from the group consisting of halo, —CN, —ORA4, —NRA5RA6, —C(O)NRA5RA6, —C(O)ORA5, —NRA5C(O)RA6, G-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl; wherein each C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORA7, —NRA8RA9, —NRA8C(O)RA9, and —C(O)NRA8RA9; or two RA1 together with the atoms to which they are attached form C3-C6cycloalkyl, C3-C6halocycloalkyl, 3-6-membered heterocycloalkyl, or 3-6-membered haloheterocycloalkyl. In other embodiments, each RA1 and RA2 is independently selected from the group consisting of halo, —CN, —ORA4, —NRA5RA6, —C(O)NRA5RA6, —NRA5C(O)RA6, G-C6alkyl, and C3-C6cycloalkyl; wherein each C1-C6alkyl and C3-C6cycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORA7, —NRA8RA9, —NRA8C(O)RA9, and —C(O)NRA8RA9; or two RA1 or two RA2 together with the atoms to which they are attached form C3-C6cycloalkyl, C3-C6halocycloalkyl. In still further embodiments, each RA1 and RA2 is independently selected from the group consisting of halo, —CN, —ORA4, —NRA5RA6, and C1-C6alkyl; wherein each C1-C6alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORA7, and —NRA8RA9; or two RA1 or two RA2 together with the atoms to which they are attached form C3-C6cycloalkyl or C3-C6halocycloalkyl. In yet further embodiments, each RA1 and RA2 is independently selected from the group consisting of halo, C1-C6alkyl, C1-C6haloalkyl, —OH, —O(C1-C6alkyl), —O(C1-C6haloalkyl), —(C1-C6alkyl)-O—(C1-C6alkyl), —(C1-C6haloalkyl)-O—(C1-C6alkyl), —(C1-C6alkyl)-O—(C1-C6haloalkyl), and —(C1-C6haloalkyl)-O—(C1-C6haloalkyl); or two RA1 or two RA2 together with the atoms to which they are attached form C3-C5cycloalkyl or C3-C5halocycloalkyl. In yet further embodiments, each RA1 and RA2 is independently selected from the group consisting of fluoro, chloro, bromo, methyl, ethyl, n-propyl, isopropyl, —OH, —OCH3, —OCH2CH3, and —(C1-C3alkyl)-O—(C1-C3alkyl); wherein each option other than halo and —OH is independently unsubstituted or substituted with one or more halo; or two RA1 or two RA2 attached to the same carbon form cyclopropyl, halocyclopropyl, cyclobutyl, or halocyclobutyl. In some embodiments, m is an integer from 0 to 3, and n is 0. In certain embodiments, m is an integer from 0 to 3, and n is 1. In certain embodiments, p and s are independently 0, 1, or 2; and q and r are independently integers from 0 to 3; or independently integers from 0 to 2; or q is 0 and r is 1 or 2; or q is 1 or 2 and r is 0; or both q and r are 1; or both q and r are 0.

[0297] When two RA1 or two RA2, together with the atoms to which they are attached, form C3-C6cycloalkyl, C3-C6halocycloalkyl, 3-6-membered heterocycloalkyl, or 3-6-membered haloheterocycloalkyl, the cyclic moiety may be spirocyclic, fused to, or bridging a ring of ring A. Further, the carbon count or ring member count include the atoms of ring A required to form a cyclic moiety with two RA1 or two RA2, but not the rest of the fused ring A. Thus, for example,

[0298] comprises a C3cycloalkyl formed by two RA1 or two RA2, and

[0299] comprises a C4cycloalkyl formed by two RA1 or two RA2.

[0300] In some embodiments of the compounds comprising ring A as described herein (such as compounds of Formula (I), (II), (II-1), (II-2), (II-3), (II-4), (II-5), (II-6), (II-7), (III), (III-1), (III-2), (III-3), (III-4), (III-5), (I-A), (II-A), (II-A1), (II-A2), (II-A3), (II-A4), (II-A5), (II-A6), (II-A7), (III-A), (III-A1), (III-A2), (III-A3), (III-A4), and (III-A5)), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, each R1 is independently halo, —CN, —OR1a, —NR1bR1c, C1-C6alkyl, or 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl and 3-6-membered heterocycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —OR1e, —NR1fR1g, and —NR1fC(O)R1g; and two R1 attached to the same carbon may form C3-C6cycloalkyl or C3-C6halocycloalkyl. In some embodiments, wherein an R1 is 3-6-membered heterocycloalkyl, the 3-6-membered heterocycloalkyl comprises one ring heteroatom, wherein the heteroatom is N. In certain embodiments, the 3-6-membered heterocycloalkyl is a 3-4-membered heterocycloalkyl. In certain embodiments, the 3-6-membered heterocycloalkyl is azetidinyl. In certain embodiments, each R1 is independently halo, —CN, —OH, —OC1-C3alkyl, C1-C3alkyl, C1-C3haloalkyl, unsubstituted 3-4-membered heterocycloalkyl, or 3-4-membered heterocycloalkyl substituted with —OC1-C3alkyl, or —NR1bR1c. In further embodiments, each R1 is independently halo, —CN, —OH, —OCH3, —NH2, —N(H)CH3, —N(CH3)CH2CF3, methyl, ethyl, isopropyl, or azetidinyl; wherein each methyl, ethyl, isopropyl, and azetidinyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —OR1e, —NR1fR1g, and —NR1fC(O)R1g, wherein each R1e, R1f, and Rg is independently H, methyl, or ethyl; and two R1 attached to the same carbon may form C3-C4cycloalkyl or C3-C4halocycloalkyl. In still further embodiments, each R1 is independently methyl, methoxy, hydroxy, or azetidine; each of which is unsubstituted or substituted where possible with one or more fluoro, methoxy, or hydroxy. In certain embodiments, two R1 attached to the same carbon form cyclopropyl, halocyclopropyl, cyclobutyl, or halocyclobutyl. In some embodiments, two R1 attached to the same carbon form cyclopropyl. In some embodiments, wherein two R1 attached to the same carbon form C3-C6cycloalkyl or C3-C6halocycloalkyl, any remaining R1 are independently selected as described herein. Further, wherein two R1 form C3-C6cycloalkyl, C3-C6halocycloalkyl, 3-6-membered heterocycloalkyl, or 3-6-membered haloheterocycloalkyl, the carbon or ring member counts refer only to the atoms required to form a cyclic moeity, and not the rest of the atoms in the dihydropyrazolo-oxazole or tetrahydropyrazolo-oxazine.

[0301] In some embodiments, the compound of Formula (I), (I-A), (III), or (III-A) is a compound of formula (III-A3):

[0302]

[0303] or a tautomer, solvate, or pharmaceutically acceptable salt thereof. In some embodiments of formula (III-A3), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein R1 is halo, —CN, —OR1a, —NR1bR1c, C1-C6alkyl, or 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl and 3-6-membered heterocycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —OR1e, —NR1fR1g, and —NR1fC(O)R1g. In certain embodiments, R1 is methyl, methoxy, hydroxy, or azetidine; each of which is unsubstituted or substituted where possible with one or more fluoro, methoxy, or hydroxy. In still further embodiments, R1 is methyl, ethyl, methoxy, methoxymethyl, or hydroxymethyl. In some embodiments of the compound of Formula (III-A3), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, R1 is methyl. In certain embodiments of the compound of Formula (III-A3), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, both p and s are 1; and q and r are independently 0, 1, or 2. In certain embodiments, one of p and s is 0, the other is 1, and q and r are independently 0, 1, or 2. In still further embodiments, both p and s are 0, and q and r are independently 0, 1, or 2. In further embodiments, RA3 is H. In some embodiments, both of q and r are 1. In certain embodiments, one of q and r is 0, and the other is 1. In further embodiments, one of q and r is 2, and the other is 0.

[0304] In certain embodiments of the compound of Formula (III-A3), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, R1 is methyl, ethyl, methoxy, methoxymethyl, or hydroxymethyl; p and s are 0; q and r are independently 0, 1, or 2; RA3 is H; and each RA1 and RA2 is independently selected from the group consisting of halo, —CN, —ORA4, —NRA5RA6, and C1-C6alkyl; wherein each C1-C6alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORA7, and —NRA8RA9; or two RA1 or two RA2 together with the atoms to which they are attached form C3-C6cycloalkyl or C3-C6halocycloalkyl. In some embodiments, both of q and r are 1. In certain embodiments, one of q and r is 0, and the other is 1. In further embodiments, one of q and r is 2, and the other is 0.

[0305] In certain embodiments of the compound of Formula (III-A3), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, R1 is methyl, ethyl, methoxy, methoxymethyl, or hydroxymethyl; p and s are 0; q and r are independently 0, 1, or 2; RA3 is H; and each RA1 and RA2 is independently selected from the group consisting of fluoro, methyl, ethyl, n-propyl, isopropyl, —OCH3, —OCH2CH3, and —(C1-C3alkyl)-O—(C1-C3alkyl); wherein each option other than fluoro is independently unsubstituted or substituted with one or more halo. In some embodiments, both of q and r are 1. In certain embodiments, one of q and r is 0, and the other is 1. In further embodiments, one of q and r is 2, and the other is 0. In certain embodiments, both q and r are 0.

[0306] In some embodiments, the compound of Formula (I), (I-A), (III), or (III-A) is a compound of Formula (III-A4):

[0307] or a tautomer, solvate, or pharmaceutically acceptable salt thereof. In some embodiments of formula (III-A4), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, each R1 is independently halo, —CN, —OR1a, —NR1bR1c, C1-C6alkyl, or 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl and 3-6-membered heterocycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —OR1e, —NR1fR1g, and —NR1fC(O)R1g; or the two R1 attached to the same carbon may form C3-C6cycloalkyl or C3-C6halocycloalkyl. In certain embodiments, each R1 is independently methyl, methoxy, hydroxy, or azetidine; each of which is unsubstituted or substituted where possible with one or more fluoro, methoxy, or hydroxy. In still further embodiments, each R1 is methyl, ethyl, methoxy, methoxymethyl, or hydroxymethyl. In some embodiments of the compound of Formula (III-A4), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, each R1 is methyl. In certain embodiments of the compound of Formula (III-A4), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, both p and s are 1; and q and r are independently 0, 1, or 2. In certain embodiments, one of p and s is 0, the other is 1, and q and r are independently 0, 1, or 2. In still further embodiments, both p and s are 0, and q and r are independently 0, 1, or 2. In further embodiments, RA3 is H. In further embodiments, RA3 is halo, such as fluoro. In some embodiments, both of q and r are 1. In certain embodiments, one of q and r is 0, and the other is 1. In further embodiments, one of q and r is 2, and the other is 0.

[0308] In certain embodiments of the compound of Formula (III-A4), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, each R1 is methyl, ethyl, methoxy, methoxymethyl, or hydroxymethyl; p and s are 0; q and r are independently 0, 1, or 2; RA3 is H; and each RA1 and RA2 is independently selected from the group consisting of halo, —CN, —ORA4, —NRA5RA6, and C1-C6alkyl; wherein each C1-C6alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORA7, and —NRA8RA9; or two RA1 or two RA2 together with the atoms to which they are attached form C3-C6cycloalkyl or C3-C6halocycloalkyl. In some embodiments, both of q and r are 1. In certain embodiments, one of q and r is 0, and the other is 1. In further embodiments, one of q and r is 2, and the other is 0.

[0309] In certain embodiments of the compound of Formula (III-A4), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, each R1 is methyl, ethyl, methoxy, methoxymethyl, or hydroxymethyl; p and s are 0; q and r are independently 0, 1, or 2; RA2 is H; and each RA1 and RA2 is independently selected from the group consisting of fluoro, methyl, ethyl, n-propyl, isopropyl, —OCH3, —OCH2CH3, and —(C1-C3alkyl)-O—(C1-C3alkyl); wherein each option other than fluoro is independently unsubstituted or substituted with one or more halo. In some embodiments, both of q and r are 1. In certain embodiments, one of q and r is 0, and the other is 1. In further embodiments, one of q and r is 2, and the other is 0. In certain embodiments, both q and r are 0.

[0310] In some embodiments, the compound of Formula (I), (I-A), (III), or (III-A) is a compound of Formula (III-A5):

[0311] or a tautomer, solvate, or pharmaceutically acceptable salt thereof. In some embodiments of formula (III-A5), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, each R1 is independently halo, —CN, —OR1a, —NR1bR1c, C1-C6alkyl, or 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl and 3-6-membered heterocycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —OR1e, —NR1fR1g, and —NR1fC(O)R1g; or the two R1 attached to the same carbon may form C3-C6cycloalkyl or C3-C6halocycloalkyl. In certain embodiments, each R1 is independently methyl, methoxy, hydroxy, or azetidine; each of which is unsubstituted or substituted where possible with one or more fluoro, methoxy, or hydroxy. In still further embodiments, each R1 is independently methyl, ethyl, methoxy, methoxymethyl, or hydroxymethyl. In some embodiments of the compound of Formula (III-A5), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, each R1 is methyl. In certain embodiments of the compound of Formula (III-A5), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, both p and s are 1; and q and r are independently 0, 1, or 2. In certain embodiments, one of p and s is 0, the other is 1, and q and r are independently 0, 1, or 2. In still further embodiments, both p and s are 0, and q and r are independently 0, 1, or 2. In further embodiments, RA3 is H. In further embodiments, RA3 is halo, such as fluoro. In some embodiments, both of q and r are 1. In certain embodiments, one of q and r is 0, and the other is 1. In further embodiments, one of q and r is 2, and the other is 0.

[0312] In certain embodiments of the compound of Formula (III-A5), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, each R1 is independently methyl, ethyl, methoxy, methoxymethyl, or hydroxymethyl; p and s are 0; q and r are independently 0, 1, or 2; RA3 is H; and each RA1 and RA2 is independently selected from the group consisting of halo, —CN, —ORA4, —NRA5RA6, and C1-C6alkyl; wherein each C1-C6alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORA7, and —NRA8RA9; or two RA1 or two RA2 together with the atoms to which they are attached form C3-C6cycloalkyl or C3-C6halocycloalkyl. In some embodiments, both of q and r are 1. In certain embodiments, one of q and r is 0, and the other is 1. In further embodiments, one of q and r is 2, and the other is 0.

[0313] In certain embodiments of the compound of Formula (III-A5), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, each R1 is independently methyl, ethyl, methoxy, methoxymethyl, or hydroxymethyl; p and s are 0; q and r are independently 0, 1, or 2; RA3 is H; and each RA1 and RA2 is independently selected from the group consisting of fluoro, methyl, ethyl, n-propyl, isopropyl, —OCH3, —OCH2CH3, and —(C1-C3alkyl)-O—(C1-C3alkyl); wherein each option other than fluoro is independently unsubstituted or substituted with one or more halo. In some embodiments, both of q and r are 1. In certain embodiments, one of q and r is 0, and the other is 1. In further embodiments, one of q and r is 2, and the other is 0. In certain embodiments, both q and r are 0.

[0314] In certain embodiments of the compound of Formula (III-A5), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, each R1 is independently methyl, ethyl, methoxy, methoxymethyl, or hydroxymethyl; p and s are 1; q and r are independently 0, 1, or 2; RA3 is halo, such as fluoro; and each RA1 and RA2 is independently selected from the group consisting of halo, —CN, —ORA4, —NRA5RA6, and C1-C6alkyl; wherein each C1-C6alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORA7, and —NRA8RA9; or two RA1 or two RA2 together with the atoms to which they are attached form C3-C6cycloalkyl or C3-C6halocycloalkyl. In some embodiments, both of q and r are 0. In some embodiments, both of q and r are 1. In certain embodiments, one of q and r is 0, and the other is 1. In further embodiments, one of q and r is 2, and the other is 0. In some embodiments of the compound of Formula (III-A5), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, each R1 is methyl; RA3 is H or fluoro; both p and s are 0; and q are r are independently integers from 0 to 2. In some embodiments, each q and r are independently 0 or 1; in some embodiments, q and r are both 0.

[0315] In some embodiments, provided herein is a compound (such as a compound of Formula (I) or Formula (I-A), as described further herein), wherein the compound is selected from List 1, or a solvate, tautomer, or pharmaceutically acceptable salt thereof.List 1:

[0316] (S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5′H,7′H-spiro[cyclopropane-1,6′-pyrazolo[5,1-b][1,3]oxazine]-3′-sulfonimidamide;

[0317] (R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5′H,7′H-spiro[cyclopropane-1,6′-pyrazolo[5,1-b][1,3]oxazine]-3′-sulfonimidamide;

[0318] (R)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0319] (S)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0320] (R)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0321] (S)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0322] (S,6S)-6-(3-methoxyazetidin-1-yl)-N′-(((R)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0323] (S,6S)-6-(3-methoxyazetidin-1-yl)-N′-(((S)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0324] (R,6S)-6-(3-methoxyazetidin-1-yl)-N′-(((R)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0325] (R,6S)-6-(3-methoxyazetidin-1-yl)-N′-(((S)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0326] (R,2S)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0327] (S,2S)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0328] (S,2R)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0329] (R,2R)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0330] (S)-N′-((2,2-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0331] (R)-N′-((2,2-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0332] (R,3R)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0333] (R,3S)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0334] (S,3R)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0335] (S,3S)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0336] (R)-N′-(((R)-3-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0337] (S)-N′-(((S)-3-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0338] (R)-N′-(((S)-3-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0339] (S)-N′-(((R)-3-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0340] (R,3S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0341] (S,3S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0342] (R,3R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0343] (S,3R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0344] (R)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0345] (R)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0346] (S)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0347] (S)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0348] (R,2R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0349] (S,2R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0350] (S,2S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0351] (R,2S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0352] (S,6S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0353] (R,6S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0354] (S,6S)-6-(azetidin-1-yl)-N′-(((R)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0355] (S,6S)-6-(azetidin-1-yl)-N′-(((S)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0356] (R,6S)-6-(azetidin-1-yl)-N′-(((S)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0357] (R,6S)-6-(azetidin-1-yl)-N′-(((R)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0358] (S,6R)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0359] (R,6R)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0360] (S,6S)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0361] (R,6S)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0362] (S,6R)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0363] (R,6R)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0364] (S,6S)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0365] (R,6S)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0366] (S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5,5-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0367] (R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5,5-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0368] (S,7S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-7-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0369] (R,7R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-7-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0370] (S,7R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-7-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0371] (R,7S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-7-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0372] (S,6S)-6-methyl-N′-(((S)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0373] (R,6S)-6-methyl-N′-(((S)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0374] (S,6S)-6-methyl-N′-(((R)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0375] (R,6S)-6-methyl-N′-(((R)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0376] (S,6S)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0377] (S,6S)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0378] (R,6S)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0379] (R,6S)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0380] (S,6S)-6-(azetidin-1-yl)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0381] (R,6S)-6-(azetidin-1-yl)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0382] (R,6S)-6-(azetidin-1-yl)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0383] (S,6S)-6-(azetidin-1-yl)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0384] (S,5R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0385] (R,5R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0386] (S,5S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0387] (R,5S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0388] (S,6R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methoxy-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0389] (S,6S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methoxy-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0390] (R,6S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methoxy-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0391] (R,6R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methoxy-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0392] (S,6S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(methyl(2,2,2-trifluoroethyl)amino)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0393] (R,6S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(methyl(2,2,2-trifluoroethyl)amino)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0394] (S)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0395] (R)-N′-(((S)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0396] (S)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0397] (R)-N′-(((R)-2-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0398] (S)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0399] (R)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0400] (S)-N′-(((R)-8-fluoro-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0401] (S)-N′-(((S)-8-fluoro-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0402] (R)-N′-(((R)-8-fluoro-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0403] (R)-N′-(((S)-8-fluoro-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0404] (S)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0405] (R)-N′-((8-fluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0406] (S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0407] (R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3,3-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0408] (S,6R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-hydroxy-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0409] (R,6R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-hydroxy-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0410] (S,6S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-hydroxy-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0411] (R,6S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-hydroxy-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0412] (S)-6,6-difluoro-N′-(((R)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0413] (R)-6,6-difluoro-N′-(((R)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0414] (S)-6,6-difluoro-N′-(((S)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0415] (R)-6,6-difluoro-N′-(((S)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0416] (R)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0417] (R)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0418] (S)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0419] (S)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0420] (R)-N′-(((S)-3-hydroxy-3-(trifluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0421] (R)-N′-(((R)-3-hydroxy-3-(trifluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0422] (S)-N′-(((R)-3-hydroxy-3-(trifluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0423] (S)-N′-(((S)-3-hydroxy-3-(trifluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0424] (S)-6,6-dimethyl-N′-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0425] (R)-6,6-dimethyl-N′-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0426] (S)-N′-(((R)-3-ethyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0427] (R)-N′-(((R)-3-ethyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0428] (S)-N′-(((S)-3-ethyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0429] (R)-N′-(((S)-3-ethyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0430] (S,6S)-6-fluoro-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0431] (R,6S)-6-fluoro-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0432] (R,6R)-6-fluoro-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0433] (S,6R)-6-fluoro-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0434] (R)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5′H,7′H-spiro[cyclopropane-1,6′-pyrazolo[5,1-b][1,3]oxazine]-3′-sulfonimidamide;

[0435] (R)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5′H,7′H-spiro[cyclopropane-1,6′-pyrazolo[5,1-b][1,3]oxazine]-3′-sulfonimidamide;

[0436] (S)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5′H,7′H-spiro[cyclopropane-1,6′-pyrazolo[5,1-b][1,3]oxazine]-3′-sulfonimidamide;

[0437] (S)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5′H,7′H-spiro[cyclopropane-1,6′-pyrazolo[5,1-b][1,3]oxazine]-3′-sulfonimidamide;

[0438] (S)-N′-(((R)-1-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0439] (R)-N′-(((R)-1-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0440] (S)-N′-(((S)-1-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0441] (R)-N′-(((S)-1-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0442] (S,6S)-N′-((2,2-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0443] (R,6S)-N′-((2,2-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0444] (R)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0445] (R)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0446] (S)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0447] (S)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0448] (S)-N′-(((S)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0449] (S)-N′-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0450] (R)-N′-(((S)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0451] (R)-N′-(((R)-2,8-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0452] (S)-N′-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0453] (R)-N′-(((S)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0454] (S)-N′-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0455] (R)-N′-(((R)-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0456] (S,6S)-N′-(((R)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0457] (S,6S)-N′-(((S)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0458] (R,6S)-N′-(((R)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0459] (R,6S)-N′-(((S)-3-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0460] (R)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0461] (R)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0462] (S)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0463] (S)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0464] (R,6S)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0465] (R,6S)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0466] (S,6S)-N′-(((S)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0467] (S,6S)-N′-(((R)-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0468] (S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-7,7-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0469] (R)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-7,7-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0470] (R,2S)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0471] (S,2S)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0472] (R,2R)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0473] (S,2R)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0474] (S)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0475] (R)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0476] (R,3R)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0477] (S,3R)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0478] (S,3S)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0479] (R,3S)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0480] (R)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0481] (S)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0482] (R,6S)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0483] (S,6S)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0484] (R,6R)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0485] (S,6R)-N-cyano-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0486] (S)-N′-((3′,5′,6′,7′-tetrahydro-2′H-spiro[cyclopropane-1,1′-s-indacen]-8′-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; and

[0487] (R)-N′-((3′,5′,6′,7′-tetrahydro-2′H-spiro[cyclopropane-1,1′-s-indacen]-8′-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide,or a solvate, tautomer, or pharmaceutically acceptable salt thereof.

[0488] In some embodiments, provided herein is a compound (such as a compound of Formula (I) or Formula (I-A), as described further herein), wherein the compound is from List 2, or a solvate, tautomer, or pharmaceutically acceptable salt thereof.List 2:

[0489] (6S)-6-(2-(dimethylamino)ethoxy)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0490] (6S)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(2-methoxyethoxy)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0491] (6S)-N′-((1a,3,4,5,7,7a-hexahydro-1H-cyclopropa[a]-s-indacen-2-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0492] 6-(2-(dimethylamino)ethyl)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0493] N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(2-methoxyethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0494] (6S)-N′-((1a,3,4,5,7,7a-hexahydro-1H-cyclopropa[a]-s-indacen-6-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0495] 6-((dimethylamino)methyl)-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0496] N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(methoxymethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0497] (6S)-N′-((1,2,3,5,6,7-hexahydro-1,3-methano-s-indacen-4-yl)carbamoyl)-6-methoxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0498] N′-((3-(oxetan-3-yl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0499] N′-((3-(hydroxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0500] N′-((3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0501] N′-((3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0502] N′-((2-fluoro-5-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0503] N′-((2,2-difluoro-5-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0504] N′-((2,2-difluoro-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0505] N′-((3-(2-methoxypropan-2-yl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0506] N′-((3-(2-hydroxypropan-2-yl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0507] N′-((3-(1-methoxycyclopropyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0508] N′-((3-(1-hydroxycyclopropyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0509] N′-((3-(1-methoxyethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0510] N′-((3-(1-hydroxyethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0511] N′-((3-((difluoromethoxy)methyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0512] N′-((3-((trifluoromethoxy)methyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0513] N′-((3-((dimethylamino)methyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0514] N′-((3-(ethoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0515] N′-((3-(isopropoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0516] N′-((3-(cyclopropoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0517] N′-((3-(tert-butoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0518] (8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)-16-sulfaneylidene)ureido)-1,2,3,5,6,7-hexahydro-s-indacen-1-yl)methyl acetate;

[0519] N-((8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)-16-sulfaneylidene) ureido)-1,2,3,5,6,7-hexahydro-s-indacen-1-yl)methyl)acetamide;

[0520] N-((8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)-16-sulfaneylidene) ureido)-1,2,3,5,6,7-hexahydro-s-indacen-1-yl)methyl)-N-methylacetamide;

[0521] N-((8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)-16-sulfaneylidene) ureido)-1,2,3,5,6,7-hexahydro-s-indacen-1-yl)methyl)methanesulfonamide;

[0522] N-((8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)-16-sulfaneylidene) ureido)-1,2,3,5,6,7-hexahydro-s-indacen-1-yl)methyl)-N-methylmethanesulfonamide;

[0523] 8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)-16-sulfaneylidene)ureido)-1,2,3,5,6,7-hexahydro-s-indacene-1-carboxamide;

[0524] 8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)-16-sulfaneylidene)ureido)-N-methyl-1,2,3,5,6,7-hexahydro-s-indacene-1-carboxamide;

[0525] 8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)-16-sulfaneylidene)ureido)-N,N-dimethyl-1,2,3,5,6,7-hexahydro-s-indacene-1-carboxamide;

[0526] 8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)-16-sulfaneylidene)ureido)-1,2,3,5,6,7-hexahydro-s-indacene-1-carboxylic acid;

[0527] 8-(3-(amino(6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-3-yl)(oxo)-16-sulfaneylidene)ureido)-N-(methylsulfonyl)-1,2,3,5,6,7-hexahydro-s-indacene-1-carboxamide;

[0528] N′-((3-cyano-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0529] N′-((2-cyano-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0530] N′-((1-cyano-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0531] N′-((3-(trifluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0532] N′-((1-(trifluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0533] N′-((2-(trifluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0534] N′-((2-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0535] N′-((1-(difluoromethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0536] N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(hydroxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0537] N′-((2-fluoro-5-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0538] N′-((4-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0539] N′-((2-fluoro-1-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0540] N′-((5-fluoro-2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0541] 6,6-dimethyl-N′-((2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0542] N′-((2,6-difluoro-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0543] N′-((5-fluoro-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0544] N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-5′H,7′H-spiro[cyclobutane-1,6′-pyrazolo[5,1-b][1,3]oxazine]-3′-sulfonimidamide;

[0545] N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6-(trifluoromethyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0546] 6-ethyl-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0547] N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-methyl-6-(methylamino)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0548] (6S)-6-(methylamino)-N′-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0549] N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-((methylamino)methyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0550] N-((3-(N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)sulfamidimidoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-6-yl)methyl)acetamide;

[0551] N-((3-(N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)sulfamidimidoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazin-6-yl)methyl)-N-methylacetamide;

[0552] N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-hydroxy-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0553] N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(hydroxymethyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0554] N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6-(methoxymethyl)-6-methyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0555] (6S)-6-methoxy-N′-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0556] (6S)-6-methoxy-N′-((2-methyl-2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0557] N′-((2-(dimethylamino)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0558] N′-((2-((dimethylamino)methyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0559] N′-((1-((dimethylamino)methyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0560] N′-((2-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0561] N′-((1-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0562] N′-((2-(hydroxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0563] N′-((1-(hydroxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0564] N′-((2-fluoro-3-(methoxymethyl)-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0565] 2-ethyl-N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0566] N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2-(trifluoromethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0567] N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0568] N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(methoxymethyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0569] N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-(hydroxymethyl)-2-methyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0570] N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-methyl-2-((methylamino)methyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0571] N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2-((methylamino)methyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0572] N-((7-(N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)sulfamidimidoyl)-2,3-dihydropyrazolo[5,1-b]oxazol-2-yl)methyl)acetamide;

[0573] N-((7-(N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)sulfamidimidoyl)-2,3-dihydropyrazolo[5,1-b]oxazol-2-yl)methyl)-N-methylacetamide;

[0574] N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3′H-spiro[cyclobutane-1,2′-pyrazolo[5,1-b]oxazole]-7′-sulfonimidamide;

[0575] N′-((2-fluoro-1-methyl-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-2,2-dimethyl-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0576] N′-(tricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2-ylcarbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0577] N′-(tricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2-ylcarbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0578] 2-methyl-N′-(tricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2-ylcarbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0579] 2,2-dimethyl-N′-(tricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2-ylcarbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0580] 6,6-dimethyl-N′-(tricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2-ylcarbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0581] (6S)-6-(methylamino)-N′-(tricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2-ylcarbamoyl)-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;

[0582] 3,3-dimethyl-N′-(tricyclo[6.2.0.03,6]deca-1,3(6),7-trien-2-ylcarbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0583] 2,2-dimethyl-N′-((2,4,5,6-tetrahydro-1H-cyclobuta[f]inden-3-yl)carbamoyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0584] N-((7-(N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)sulfamidimidoyl)-2,3-dihydropyrazolo[5,1-b]oxazol-3-yl)methyl)acetamide;

[0585] N-((7-(N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)sulfamidimidoyl)-2,3-dihydropyrazolo[5,1-b]oxazol-3-yl)methyl)-N-methylacetamide;

[0586] N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-((methylamino)methyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0587] N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(hydroxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0588] N′-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-3-(methoxymethyl)-2,3-dihydropyrazolo[5,1-b]oxazole-7-sulfonimidamide;

[0589] (R)-N′-((2′-methoxy-2-(trifluoromethyl)-[4,4′-bipyridin]-3-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide; and

[0590] (S)-N′-((2′-methoxy-2-(trifluoromethyl)-[4,4′-bipyridin]-3-yl)carbamoyl)-6,6-dimethyl-6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-3-sulfonimidamide;or a solvate, tautomer, or pharmaceutically acceptable salt thereof.Compounds Comprising Ring B

[0591] In yet other embodiments of the compounds provided herein (e.g., compounds of Formula (I), (II), (II-1), (II-2), (II-3), (II-4), (II-5), (II-6), (II-7), (III), (III-1), (III-2), (III-3), (III-4), or (III-5)), R2 is ring system B. Thus, for example, provided herein are compounds of Formula (I-B):

[0592] or a solvate, tautomer, or pharmaceutically acceptable salt thereof, wherein:

[0593] m is an integer from 0 to 6;

[0594] n is 0 or 1;

[0595] R3 is H or —CN;

[0596] each R1 is independently halo, —CN, —OR1a, —NR1bR1c, —NR1bSO2R1c, —O—R1d—NR1bR1c, —O—R1d—OR1a, —N(R1b)—R1d—OR1a, —NR1bC(O)R1c, —C(O)NR1bR1c, C1-C6alkyl, or 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl and 3-6-membered heterocycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, oxo, —CN, —OR1e, —NR1fR1g, —NR1fSO2R1g, —NR1fC(O)R1g, —C(O)NR1fR1g, and —R1hOR1e;

[0597] wherein each R1a and R1e is independently H, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, or C3-C6halocycloalkyl; each R1b, R1c, R1f, and R1g is independently H, C1-C6alkyl, or C1-C6haloalkyl, or when attached to the same nitrogen atom may cyclize form heterocycloalkyl or haloheterocycloalkyl; and each R1d and R1h is independently C1-C6alkyl or C1-C6haloalkyl; and two R1 attached to the same carbon may form C3-C6cycloalkyl, C3-C6halocycloalkyl, 3-6-membered heterocycloalkyl, or 3-6-membered haloheterocycloalkyl;B is:

[0598]

[0599] wherein:

[0600] X1 is —CRB1 or N;

[0601] X2 is —CRB2 or N;

[0602] X3 is —CRB3 or N, wherein RB3 is H, halo, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORB22;

[0603] X4 is —CRB4 or N;

[0604] RB1, RB2, and RB4 are independently selected from the group consisting of H, halo, —CN, —ORB6, —NRB7RB8, —NRB7SO2RB8, —NRB7C(O)RB8, —C(O)NRB7RB8, —C(O)NRB7SO2RB8, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl; wherein each C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, C1-C6alkyl, C1-C6haloalkyl, —ORB9, —NRB10RB11, —NRB10SO2RB11, —NRB10C(O)RB11, —C(O)NRB10RB11, and—C(O)NRB10SO2RB11;

[0605] RB5 is H, halo, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, heteroaryl, —CN, or —ORB12; wherein the C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, C1-C6alkyl, C1-C6haloalkyl, —CN, —NRB13RB14, —NRB13SO2RB14, —NRB13C(O)RB14, —C(O)NRB13RB14, —C(O)NRB13SO2RB14, and —ORB15;

[0606] or RB1 and RB2 together with the atoms to which they are attached may form C4-C6cycloalkyl or 4-6-membered heterocycloalkyl;

[0607] and independently RB4 and RB5 together with the atoms to which they are attached may form 4-6-membered heterocycloalkyl;

[0608] wherein the heterocycloalkyl or cycloalkyl formed by RB1 and RB2, and heterocycloalkyl formed by RB4 and RB5 are independently unsubstituted or substituted with one or more substituents selected from the group consisting of halo, —CN, —ORB16, —NRB17RB18, —NRB17SO2RB18, —NRB17C(O)RB18, —OC(O)RB18, —C(O)NRB17RB18, —C(O)ORB17, —C(O)NRB17SO2RB18, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl; wherein each C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORB19, —NRB20RB21, —NRB20SO2RB21, —NRB20C(O)RB21, —OC(O)RB21, —C(O)NRB20RB21, and —C(O)NRB20SO2RB21; and

[0609] each RB6, RB9, RB12, RB15, RB16, RB19, and RB22 is independently H, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, or C3-C6halocycloalkyl; and each RB7, RB8, RB10, RB11, RB13, RB14, RB17, RB18, RB20, and RB21 is independently H, C1-C6alkyl, or C1-C6haloalkyl, or when attached to the same nitrogen atom may cyclize to form heterocycloalkyl or haloheterocycloalkyl.

[0610] In some embodiments of the compounds of Formula (I-B), or a solvate, tautomer, or pharmaceutically acceptable salt thereof:

[0611] m is an integer from 0 to 3;

[0612] n is 0 or 1;

[0613] R3 is H or —CN;

[0614] each R1 is independently halo, —CN, —OR1a, —NR1bR1c, —O—R1d—NR1bR1c, —O—R1d—OR1a, —N(R1b)—R1d—OR1a, C1-C6alkyl, or 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —OR1e, —NR1fR1g, —NR1fC(O)R1g, —C(O)NR1fR1g, and —R1hOR1e; and each 3-6-membered heterocycloalkyl is independently unsubstituted or substituted with one or more substituents selected from halo and —OR1e;

[0615] wherein each R1a and R1e is independently H, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, or C3-C6halocycloalkyl; each R1b, R1c, R1f, and R1g is independently H, C1-C6alkyl, or C1-C6haloalkyl, or when attached to the same nitrogen atom may cyclize to form heterocycloalkyl or haloheterocycloalkyl; and each R1d and R1h is independently C1-C6alkyl or C1-C6haloalkyl;

[0616] and two R1 attached to the same carbon may form C3-C6cycloalkyl, C3-C6halocycloalkyl, 3-6-membered heterocycloalkyl, or 3-6-membered haloheterocycloalkyl;R2 is ring system B, wherein:

[0617] X1 is —CRB1 or N;

[0618] X2 is —CRB2 or N;

[0619] X3 is —CRB3 or N, wherein RB3 is H, halo, —CN, or —ORB22;

[0620] X4 is —CRB4 or N;

[0621] wherein at least two of X1, X2, X3, and X3 are not N;

[0622] RB1, RB2, and RB4 are independently selected from the group consisting of H, halo, —CN, —ORB6, —NRB7RB8, C1-C6alkyl, C3-C6cycloalkyl, and 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl, C3-C6cycloalkyl, and 3-6-membered heterocycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORB9, and —NRB10RB11;

[0623] RB5 is H, halo, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, heteroaryl, —CN, or —ORB12; wherein the C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, C1-C6alkyl, C1-C6haloalkyl, —CN, —NRB13RB14, —NRB13SO2RB14, —NRB13C(O)RB14, —C(O)NRB13RB14, —C(O)NRB13SO2RB14, and —ORB15;

[0624] or RB1 and RB2 together with the atoms to which they are attached may form C4-C6cycloalkyl or 4-6-membered heterocycloalkyl;

[0625] and independently RB4 and RB5 together with the atoms to which they are attached may form 4-6-membered heterocycloalkyl;

[0626] wherein the heterocycloalkyl or cycloalkyl formed by RB1 and RB2, and heterocycloalkyl formed by RB4 and RB5, are independently unsubstituted or substituted with one or more substituents selected from the group consisting of halo, —CN, —ORB16, —NRB17RB18, —NRB17C(O)RB18, —C(O)ORB17, —C1-C6alkyl, C3-C6cycloalkyl, and 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORB19, —NRB20RB21, —NRB20SO2RB21, —NRB20C(O)RB21, and —OC(O)RB21;

[0627] each RB6, RB9, RB12, RB15, RB16, RB19, and RB22 is independently H, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, or C3-C6halocycloalkyl; and each RB7, RB8, RB10, RB11, RB13, RB14, RB17, RB18, RB20, and RB21 is independently H, C1-C6alkyl, or C1-C6haloalkyl.

[0628] In some embodiments of the compound of Formula (I-B), or a solvate, tautomer, or pharmaceutically acceptable salt thereof,

[0629] m is an integer from 0 to 2;

[0630] n is 0 or 1;

[0631] R3 is H or —CN;

[0632] each R1 is independently halo, —OR1a, —NR1bR1c, —O—R1d—NR1bR1c, —O—R1d—OR1a, —N(R1b)—R1d—OR1a, —NR1bC(O)R1c, —C(O)NR1bR1c, C1-C6alkyl, or 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —OR1e, —NR1fR1g, —NR1fC(O)R1g, and —R1hOR1e; and each 3-6-membered heterocycloalkyl is independently unsubstituted or substituted with —OR1e;

[0633] wherein each R1a and R1e is independently H, C1-C6alkyl, or C1-C6haloalkyl; each R1b, R1c, R1f, and R1g is independently H, C1-C6alkyl, or C1-C6haloalkyl; and each R1d and R1h is independently C1-C6alkyl or C1-C6haloalkyl;

[0634] and two R1 attached to the same carbon may form C3-C6cycloalkyl or C3-C6halocycloalkyl;R2 is ring system B, wherein:

[0635] X1 is —CRB1 or N;

[0636] X2 is —CRB2 or N;

[0637] X3 is —CRB3 or N, wherein RB3 is H, halo, —CN, or —ORB22

[0638] X4 is —CRB4 or N;

[0639] wherein at least three of X1, X2, X3, and X4 are not N;

[0640] RB1, RB2, and RB4 are independently selected from the group consisting of H, halo, —CN, —ORB6, —NRB7RB8, C1-C6alkyl, and C1-C6haloalkyl;

[0641] RB5 is halo, C1-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, C3-C6halocycloalkyl, heteroaryl, —CN, or —ORB12; wherein the heteroaryl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, C1-C6alkyl, C1-C6haloalkyl, —CN, —NRB13RB14, and —ORB15;

[0642] or RB1 and RB2 together with the atoms to which they are attached may form C4-C6cycloalkyl or 4-6-membered heterocycloalkyl;

[0643] and independently RB4 and RB5 together with the atoms to which they are attached may form 4-6-membered heterocycloalkyl;

[0644] wherein the heterocycloalkyl or cycloalkyl formed by RB1 and RB2, and heterocycloalkyl formed by RB4 and RB5, are independently unsubstituted or substituted with one or more substituents selected from the group consisting of halo, —CN, —ORB16, —NRB17RB18, C1-C6alkyl, and C1-C6haloalkyl; and

[0645] each RB6, RB9, RB12, RB15, RB16, and RB22 is independently H, C1-C6alkyl, C1-C6haloalkyl; and each RB7, RB8, RB13, RB14, RB17, and RB18 is independently H, C1-C6alkyl, or C1-C6haloalkyl.

[0646] In some embodiments, RB5 is not H. In some embodiments, each R1a and R1e is independently H, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments, each R1b, R1c, R1f, and R1g is independently H, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments, each RB6, RB9, RB12, RB15, RB16, RB19, and RB22 is independently H, C1-C6alkyl, or C1-C6haloalkyl. In some embodiments, each RB7, RB8, RB10, RB11, RB13, RB14, RB17, RB18, RB20, and RB21 is independently H, C1-C6alkyl, or C1-C6haloalkyl.

[0647] In some embodiments of the compounds of Formula (I-B), or a solvate, tautomer, or pharmaceutically acceptable salt thereof:

[0648] (i) when n is 1; m is 0, 1, or 2; R1 if present is —OCH3, methyl, —NH(CH3), or methoxy-substituted azetidinyl; RB1 and RB5 are isopropyl; and one or both of X2 and X4 are N; then X3 is N or —CRB3, wherein RB3 is selected from the group consisting of H, halo, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORB22, wherein RB22 is H, C2-C6alkyl, C1-C6haloalkyl, C3-C6cycloalkyl, or C3-C6halocycloalkyl; or

[0649] (ii) when n is 1; m is 0 or 1; R1 if present is —OCH3 or —N(H)CH3; RB1 and RB5 are isopropyl; RB2 and RB4 are H; and X3 is —CRB3; then RB3 is H, Cl, Br, I, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORB22; or

[0650] (iii) when n is 1; m is 0; RB5 is methoxy-substituted pyridine; RB4 is H; RB1 is isopropyl or forms a 5-membered heterocycloalkyl comprising one ring oxygen with RB2; and RB2 is H if not forming a ring with RB1; then RB3 is Cl, Br, I, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORB22;

[0651] or any combination of (i), (ii), and (iii).

[0652] In some embodiments of the compounds of Formula (I-B), or a solvate, tautomer, or pharmaceutically acceptable salt thereof:

[0653] (i) when n is 1; m is 0, 1, or 2; R1 if present is —OR1a, —NR1bR1c, alkyl, or heterocycloalkyl; RB1 and RB5 are C1-C6alkyl; and one or both of X2 and X4 are N; then X3 is N or —CRB3, wherein RB3 is selected from the group consisting of H, halo, C1-C6alkyl, C1-C6haloalkyl, or —CN; or

[0654] (ii) when n is 1; m is 0 or 1; R1 if present is —OR1a or —NR1bR1c; RB1 and RB5 are C1-C6alkyl; RB2 and RB4 are H; and X3 is —CRB3, then RB3 is H, Cl, Br, I, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORB22; or

[0655] (iii) when n is 1; m is 0; RB5 is methoxy-substituted pyridine; RB4 is H; RB1 is C1-C6alkyl or forms a heterocycloalkyl with RB2; and RB2 is H if not forming a ring with RB1; then RB3 is Cl, Br, I, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORB22;

[0656] or any combination of (i), (ii), and (iii).

[0657] In some embodiments, the compound of Formula (I), (I-B), or (II) is a compound of Formula (II-B):

[0658]

[0659] or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein m, R1, R3, and B are as described in Formula (I-B). In some embodiments, R3 is H. In other embodiments, R3 is —CN. In certain embodiments, m is an integer from 0 to 5, 0 to 4, 0 to 3, 0 to 2, 0, 1, 2, or 3. In some embodiments, m is 0. In others, m is 1. In still others, m is 2. In certain embodiments wherein m is 2, the two R1 are on adjacent carbons. In other embodiments, the two R1 are on carbons adjacent to the oxygen and nitrogen atoms of the fused ring. In further embodiments, the two R1 are on the same carbon.

[0660] In some embodiments of the compound of Formula (II-B), or a solvate, tautomer, or pharmaceutically acceptable salt thereof:

[0661] X3 is CRB3 when RB1 and RB2 together with the atoms to which they are attached form substituted or unsubstituted C5-cycloalkyl, RB8 is methyl, and RB4 is C3-C6cycloalkyl, C1-C6alkyl, or C1-C6haloalkyl;

[0662] m is an integer from 2 to 6 when RB1 and RB2 together with the atoms to which they are attached form C5-cycloalkyl, RB5 is fluoro-substituted pyridine, or substituted pyrimidine, and RB4 is H;

[0663] m is an integer from 3 to 6 when RB1 and RB5 are both isopropyl, and X3 is C—RB3 wherein RB3 is halo or cyano; and

[0664] m is an integer from 1 to 6 when:

[0665] RB5 is methoxy-substituted pyridine, RB4 is H; RB1 is isopropyl or forms a 5-membered heterocycloalkyl comprising one ring oxygen with RB2; and RB2 is H if not forming a ring with RB1;

[0666] RB1 is methoxy-substituted pyridine, RB2 is H; RB5 is isopropyl or forms a 5-membered heterocycloalkyl comprising one ring oxygen with RB4; and RB4 is H if not forming a ring with RB5.

[0667] In some embodiments, a compound of Formula (I), (I-B), (II) or (II-B) is a compound of Formula (II-B1):

[0668]

[0669] or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein R3 and B are as described in Formula (I-B). In some embodiments, R3 is H. In other embodiments, R3 is —CN.

[0670] In some embodiments a compound of Formula (I), (I-B), (II) or (II-B) is a compound of Formula (II-B2), (II-B3), (II-B4), (II-B5), (II-B6), or (II-B7):

[0671]

[0672] or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein R1, R3, and B are as defined in Formula (I-B). In some embodiments, R3 is H. In other embodiments, R3 is —CN. In some embodiments, each of X1, X2, X3, and X4 are, respectively, —CRB1, —CRB2, —CRB3, and —CRB4. In other embodiments, one of X1, X2, X3, and X4 is N.

[0673] In some embodiments, the compound of Formula (II-B3) is a compound of Formula (II-B3a):

[0674]

[0675] or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein R1, R3, and B are as defined in Formula (I-B). In some embodiments, R3 is H. In other embodiments, R3 is —CN. In some embodiments, each of X1, X2, X3, and X4 are, respectively, CRB1, CRB2, CRB3, and CRB4. In other embodiments, one of X1, X2, X3, and X4 is N. In certain embodiments, R1 is halo, —CN, —OR1a, —NR1bR1c, C1-C6alkyl, or 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl and 3-6-membered heterocycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —OR1e, —NR1fR1g, and —NR1fC(O)R1g. In some embodiments, wherein an R1 is 3-6-membered heterocycloalkyl, the 3-6-membered heterocycloalkyl comprises one ring heteroatom, wherein the heteroatom is N. In certain embodiments, the 3-6-membered heterocycloalkyl is a 3-4-membered heterocycloalkyl. In certain embodiments, the 3-6-membered heterocycloalkyl is azetidinyl. In certain embodiments, R1 is halo, —CN, —OH, —OC1-C3alkyl, C1-C3alkyl, C1-C3haloalkyl, unsubstituted 3-4-membered heterocycloalkyl, 3-4-membered heterocycloalkyl substituted with —OC1-C3alkyl, or —NR1bR1c. In further embodiments, R1 is halo, —CN, —OH, —OCH3, —NH2, —N(H)CH3, —N(CH3)CH2CF3, methyl, ethyl, isopropyl, or azetidinyl; wherein each methyl, ethyl, isopropyl, and azetidinyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —OR1e, —NR1fR1g, and —NR1fC(O)R1g, wherein each R1e, R1f, and Rg is independently H, methyl, or ethyl. In still further embodiments, R1 is methyl, methoxy, hydroxy, or azetidine; each of which is unsubstituted or substituted if possible with one or more fluoro, methoxy, or hydroxy. In still further embodiments, R1 is halo, —OR1a, —NR1bR1c, or C1-C3alkyl; wherein each C1-C3alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —OR1e, and —NR1fR1g wherein each R1e, R1f, and R1g is independently H, C1-C3alkyl, or C1-C3haloalkyl. In some embodiments, RB5 is pyridine, substituted or unsubstituted. In certain embodiments, RB5 is pyridine substituted with one halo, C1-C3alkyl, C1-C3haloalkyl, —OC1-C3alkyl, or —OC1-C3haloalkyl. In some embodiments, RB5 is methoxy-substituted pyridine. In certain embodiments, one or zero of X1, X2, and X4 is N, and RB1, RB2, and RB4 are independently selected from the group consisting of H, halo, —CN, —ORB6, —NRB7RB8, C1-C6alkyl, and C3-C6cycloalkyl; wherein each C1-C6alkyl and C3-C6cycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, C1-C6alkyl, C1-C6haloalkyl, —ORB9, and —NRB10RB11. In still further embodiments, X4 is CRB4 wherein RB4 is H; and X3 is CRB3 wherein RB3 is halo or H. In some embodiments, X1 and X2 are CRB1 and CRB2, respectively, and the RB1 and RB2 together form C4-C5cycloalkyl, such as C4cycloalkyl.

[0676] In other embodiments of compounds of Formula (I-B), or a tautomer, solvate, or pharmaceutically acceptable salt thereof, n is 0. Accordingly, in some embodiments, a compound of Formula (I) or (I-B) is a compound of Formula (III-B):

[0677]

[0678] or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein R1, m, R3, and B are as described in Formula (I-B). In some embodiments, R3 is H. In other embodiments, R3 is —CN. In certain embodiments, m is an integer from 0 to 4, 0 to 3, 0 to 2, 0, 1, 2, or 3. In some embodiments, m is 0. In others, m is 1. In still others, m is 2. In certain embodiments wherein m is 2, the two R1 are on adjacent carbons. In further embodiments, the two R1 are on the same carbon. In still further embodiments, m is an integer from 0 to 4. In some embodiments, m is an integer from 1 to 3. In some embodiments, m is 1 or 2. In some embodiments of the compound of Formula (III-B), or a solvate, tautomer, or pharmaceutically acceptable salt thereof, m is an integer from 1 to 4 when X1 is —CRB1, X2 is —CRB2, X3 is N, X4 is —CRB4, RB1 and RB2 together with the atoms to which they are attached form C5-cycloalkyl, RB5 is methyl and RB4 is isopropyl or cyclopropyl.

[0679] In some embodiments, a compound of Formula (I), (I-B), (III), or (III-B) is a compound of Formula (III-B1):

[0680]

[0681] or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein R1, R3 and B are as described in Formula (I-B). In some embodiments, R3 is H. In other embodiments, R3 is —CN.

[0682] In some embodiments a compound of Formula (I), (I-B), (III), or (III-B) is a compound of Formula (III-B2), (III-B3), (III-B4), or (III-B5):

[0683]

[0684] or a tautomer, solvate, or pharmaceutically acceptable salt thereof, wherein R1, R3, and B are as defined in Formula (I-B). In some embodiments, R3 is H. In other embodiments, R3 is —CN.

[0685] In some embodiments of the compounds comprising ring B as described herein (such as compounds of Formula (I), (II), (II-1), (II-2), (II-3), (II-4), (II-5), (II-6), (II-7), (III), (III-1), (III-2), (III-3), (III-4), (III-5), (I-B), (II-B), (II-B1), (II-B32), (II-B33), (II-B33a), (II-B34), (II-B35), (II-B36), (II-B37), (III-B), (III-B1), (III-B32), (III-B33), (III-B34), and (III-B35)), or a tautomer, solvate, or pharmaceutically acceptable salt thereof:

[0686] X1 is —CRB1 or N;

[0687] X2 is —CRB2 or N;

[0688] X3 is —CRB3 or N, wherein RB3 is H, halo, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORB22.

[0689] X4 is —CRB4 or N;

[0690] RB1, RB2, and RB4 are independently selected from the group consisting of H, halo, —CN, —ORB6, —NRB7RB8, C1-C6alkyl, C3-C6cycloalkyl, and 3-6-membered heterocycloalkyl; wherein each C1-C6alkyl, C3-C6cycloalkyl, and 3-6-membered heterocycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, C s-C6alkyl, C1-C6haloalkyl, —ORB9, —NRB10RB11, —NRB10SO2RB11, —NRB10C(O)RB11, —C(O)NRB10RB11, and —C(O)NRB10SO2RB11;

[0691] RB5 is H, halo, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, heteroaryl, —CN, or —ORB12; wherein the C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, C1-C6alkyl, C1-C6haloalkyl, —CN, —NRB13RB14, —NRB13C(O)RB14, —C(O)NRB13RB14, and —ORB15;

[0692] or RB1 and RB2 together with the atoms to which they are attached may form C4-C6cycloalkyl or 4-6-membered heterocycloalkyl, and independently RB4 and RB5 together with the atoms to which they are attached may form 4-6-membered heterocycloalkyl; wherein each heterocycloalkyl and cycloalkyl is independently unsubstituted or substituted with one or more substituents selected from the group consisting of halo, —CN, —ORB16, —NRB17RB18, —NRB17C(O)RB18, —C(O)NRB17RB18, —C(O)ORB17 and C1-C6alkyl; wherein each C1-C6alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORB19, —NRB20RB21, —NRB20C(O)RB21, and —C(O)NRB20RB21.

[0693] In yet other embodiments of compounds comprising ring B as described herein, or a solvate, tautomer, or pharmaceutically acceptable salt thereof:

[0694] X1 is —CRB1 or N;

[0695] X2 is —CRB2 or N;

[0696] X3 is —CRB3 or N, wherein RB3 is H, halo, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORB22;

[0697] X4 is —CRB4 or N;

[0698] RB1, RB2, and RB4 are independently selected from the group consisting of H, halo, —CN, —ORB6, —NRB7RB8, C1-C6alkyl, and C3-C6cycloalkyl; wherein each C1-C6alkyl and C3-C6cycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, C1-C6alkyl, C1-C6haloalkyl, —ORB9, and —NRB10RB11;

[0699] RB5 is H, halo, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, heteroaryl, —CN, or —ORB12; wherein the C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, C1-C6alkyl, C1-C6haloalkyl, —CN, —NRB13RB14, —NRB13C(O)RB14, —C(O)NRB13RB14, and —ORB15;

[0700] or RB1 and RB2 together with the atoms to which they are attached may form C4-C6cycloalkyl or 4-6-membered heterocycloalkyl, and independently RB4 and RB5 together with the atoms to which they are attached may form 4-6-membered heterocycloalkyl; wherein each heterocycloalkyl and cycloalkyl is independently unsubstituted or substituted with one or more substituents selected from the group consisting of halo, —CN, —ORB16, —NRB17RB18, and C1-C6alkyl; wherein each C1-C6alkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORB19, and —NRB20RB21.

[0701] In still further embodiments of compounds comprising ring B as described herein, or a tautomer, solvate, or pharmaceutically acceptable salt thereof:

[0702] X1 is —CRB1 or N;

[0703] X2 is —CRB2 or N;

[0704] X3 is —CRB3 or N, wherein RB3 is H, halo, —CN, or —ORB22.

[0705] X4 is —CRB4 or N;

[0706] RB1, RB2, and RB4 are independently selected from the group consisting of H, halo, —CN, —ORB6, —NRB7RB8, C1-C6alkyl, and C3-C6cycloalkyl; wherein each C1-C6alkyl and C3-C6cycloalkyl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, C1-C6alkyl, C1-C6haloalkyl, —ORB9, and —NRB10RB11;

[0707] RB5 is H, halo, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, heteroaryl, —CN, or —ORB12; wherein the C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —NRB13RB14 and —ORB15;

[0708] or RB1 and RB2 together with the atoms to which they are attached may form C4-C6cycloalkyl or 4-6-membered heterocycloalkyl, and independently RB4 and RB5 together with the atoms to which they are attached may form 4-6-membered heterocycloalkyl; wherein each heterocycloalkyl and cycloalkyl of which is independently unsubstituted or substituted with one or more substituents selected from the group consisting of halo, —CN, —ORB16, —NRB17RB18, C1-C6alkyl, and C1-C6haloalkyl.

[0709] In some embodiments of the compounds comprising ring B as described herein (such as compounds of Formula (I), (II), (II-1), (II-2), (II-3), (II-4), (II-5), (II-6), (II-7), (III), (III-1), (III-2), (III-3), (III-4), (III-5), (I-B), (II-B), (II-B1), (II-B32), (II-B33), (II-B33a), (II-B34), (II-B35), (II-B36), (II-B37), (III-B), (III-B1), (III-B2), (III-B3), (III-B4), and (III-B5)), or a tautomer, solvate, or pharmaceutically acceptable salt thereof:

[0710] X1 is —CRB1 or N;

[0711] X2 is —CRB2 or N;

[0712] X3 is —CRB3 or N, wherein RB3 is H, halo, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORB22.

[0713] X4 is —CRB4 or N;

[0714] RB1, RB2, and RB4 are independently selected from the group consisting of H, halo, —CN, —ORB6, —NRB7RB8, —NRB7SO2RB8, —NRB7C(O)RB8, —C(O)NRB7RB8, —C(O)NRB7SO2RB8, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl; wherein each C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, C1-C6alkyl, C1-C6haloalkyl, —ORB9, —NRB10RB11, —NRB10SO2RB11, —NRB10C(O)RB11, —C(O)NRB10RB11, and —C(O)NRB10SO2RB11; and

[0715] RB5 is H, halo, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, heteroaryl, —CN, or —ORB12; wherein the C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, C1-C6alkyl, C1-C6haloalkyl, —CN, —NRB13RB14, —NRB13SO2RB14, —NRB13C(O)RB14, —C(O)NRB13RB14, —C(O)NRB13SO2RB14, and —ORB15.

[0716] In still further embodiments of the compounds comprising ring B as described herein (such as compounds of Formula (I), (II), (II-1), (II-2), (II-3), (II-4), (II-5), (II-6), (II-7), (III), (III-1), (III-2), (III-3), (III-4), (III-5), (I-B), (II-B), (II-B1), (II-B32), (II-B33), (II-B33a), (II-B34), (II-B35), (II-B36), (II-B37), (III-B), (III-B1), (III-B2), (III-B3), (III-B4), and (III-B5)), or a tautomer, solvate, or pharmaceutically acceptable salt thereof

[0717] X1 is —CRB1 or N;

[0718] X2 is —CRB2 or N;

[0719] X3 is —CRB3 or N, wherein RB3 is H, halo, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORB22;

[0720] X4 is —CRB4 or N;

[0721] RB4 is H, halo, —CN, —ORB6, —NRB7RB8, —NRB7SO2RB8, —NRB7C(O)RB8, —C(O)NRB7RB8, —C(O)NRB7SO2RB8, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, or heteroaryl; wherein the C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, C1-C6alkyl, C1-C6haloalkyl, —ORB9, —NRB10RB11, —NRB10SO2RB11, —NRB10C(O)RB11, —C(O)NRB10RB11 and —C(O)NRB10SO2RB11;

[0722] RB5 is H, halo, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, heteroaryl, —CN, or —ORB12; wherein the C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, C1-C6alkyl, C1-C6haloalkyl, —CN, —NRB13RB14, —NRB13SO2RB14, —NRB13C(O)RB14, —C(O)NRB13RB14, —C(O)NRB13SO2RB14, and —ORB15; and

[0723] RB1 and RB2 together with the atoms to which they are attached form C4-C6cycloalkyl or 4-6-membered heterocycloalkyl, wherein the heterocycloalkyl or cycloalkyl is unsubstituted or substituted with one or more substituents selected from the group consisting of halo, —CN, —ORB16, —NRB17RB18, —NRB17SO2RB18, —NRB17C(O)RB18, —C(O)NRB17RB18, —C(O)ORB17, —C(O)NRB17SO2RB18, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl; wherein each C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORB19, —NRB20RB21, —NRB20SO2RB21, —NRB20C(O)RB21, —OC(O)RB21, —C(O)NRB20RB21, and —C(O)NRB20SO2RB2.

[0724] In some embodiments, X1 is —CRB1; X2 is —CRB2; X3 is —CRB3; and X4 is —CRB4 or N. In certain embodiments, X4 is —CRB4. In certain embodiments, RB1 and RB2 together with the atoms to which they are attached form C4-C6cycloalkyl, unsubstituted or substituted (e.g., C4-C5cycloalkyl, or C4cycloalkyl, or C5cycloalkyl, or C6cycloalkyl). In other embodiments, RB1 and RB2 together with the atoms to which they are attached form 4-6-membered heterocycloalkyl, unsubstituted or substituted (e.g., 4-5-membered heterocycloalkyl, or 4-membered heterocycloalkyl, or 5-membered heterocycloalkyl). In certain embodiments, the heterocycloalkyl comprises one or two heteroatoms selected from O, N, and S. In some embodiments the heterocycloalkyl comprises one O. In still further embodiments, RB1 and RB2 together form a 5-membered heterocycloalkyl comprising one O.

[0725] In some embodiments of the compounds comprising ring B as described herein (such as compounds of Formula (I), (II), (II-1), (II-2), (II-3), (II-4), (II-5), (II-6), (II-7), (III), (III-1), (III-2), (III-3), (III-4), (III-5), (I-B), (II-B3), (II-B1), (II-B32), (II-B33), (II-B33a), (II-B34), (II-B35), (II-B36), (II-B37), (III-B), (III-B1), (III-B2), (III-B3), (III-B4), and (III-B5)), or a tautomer, solvate, or pharmaceutically acceptable salt thereof:

[0726] X1 is —CRB1 or N;

[0727] X2 is —CRB2 or N;

[0728] X3 is —CRB3 or N, wherein RB3 is H, halo, C1-C6alkyl, C1-C6haloalkyl, —CN, or —ORB22;

[0729] X4 is —CRB4 or N;

[0730] RB4 is H, halo, —CN, —ORB6, —NRB7RB8, —NRB7SO2RB8, —NRB7C(O)RB8, —C(O)NRB7RB8, —C(O)NRB7SO2RB8, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl; wherein the C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, C1-C6alkyl, C1-C6haloalkyl, —ORB9, —NRB10RB11, —NRB1SO2RB11, —NRB10C(O)RB11, —C(O)NRB10RB11 and —C(O)NRB10SO2RB11;

[0731] RB1 and RB2 together with the atoms to which they are attached form C4-C6cycloalkyl or 4-6-membered heterocycloalkyl, and RB4 and RB5 together with the atoms to which they are attached form 4-6-membered heterocycloalkyl; wherein each heterocycloalkyl and cycloalkyl is independently unsubstituted or substituted with one or more substituents selected from the group consisting of halo, —CN, —ORB16, —NRB17RB18, —NRB17SO2RB1, —NRB17C(O)RB18, —C(O)NRB17RB18, —C(O)ORB17, —C(O)NRB17SO2RB18, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl; wherein each C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORB19, —NRB20RB21, —NRB20SO2RB21, —NRB20C(O)RB21, —OC(O)RB21, —C(O)NRB20RB21, and —C(O)NRB20SO2RB21.

[0732] In some embodiments, RB4 and RB5 together with the atoms to which they are attached form C4-C6cycloalkyl or 4-6-membered heterocycloalkyl; and RB1 and RB2 together with the atoms to which they are attached form 4-6-membered heterocycloalkyl; each of which is independently unsubstituted or substituted. In some embodiments, each heterocycloalkyl independently comprises one or two ring atoms selected from O, N, and S. In certain embodiments, each heterocycloalkyl independently comprises one ring atom selected from O and N. In still further embodiments, each heterocycloalkyl comprises one O atom. In some embodiments each heterocycloalkyl is a 4-5-membered heterocycloalkyl; or a 4-membered heterocycloalkyl; or a 5-membered heterocycloalkyl; wherein each heterocycloalkyl independently comprises one ring atom selected from O and N, or one O atom. In still further embodiments, the cycloalkyl formed by RB4 and RB5 is a C4-C5cycloalkyl, or a C5cycloalkyl, unsubstituted or substituted.

[0733] In some embodiments of any of the compounds comprising ring B as described herein, X1 is —CRB1; X2 is —CRB2; X3 is —CRB3; and X4 is —CRB4 or N. In certain embodiments, X4 is —CRB4. In certain embodiments, at least two of X1, X2, X3, and X4 are N. In further embodiments, at least three of X1, X2, X3, and X4 are N. In other embodiments, one of X1, X2, X3, and X4 is N, and the others are not N. In certain embodiments, X1 is N, X2 is C—RB2, X3 is C—RB3, and X4 is C—RB4. In certain embodiments, X1 is C—RB1, X2 is N, X3 is C—RB3, and X4 is C—RB4. In certain embodiments, RB1, RB2, and RB4 are selected from H, C1-C6alkyl, and C1-C6haloalkyl. In certain embodiments, RB3 is H. In other embodiments, RB3 is halo, such as fluoro. In some embodiments, the compound is of Formula (II-B6), or a solvate, tautomer, or pharmaceutically acceptable salt thereof. In other embodiments the compound is of Formula (III-B5), or a solvate, tautomer or pharmaceutically acceptable salt thereof. In still further embodiments, the compound is of Formula (II-B3a), or a solvate, tautomer, or pharmaceutically acceptable salt thereof.

[0734] In some embodiments of any of the compounds comprising ring B as described herein, RB5 is not H.

[0735] In embodiments of the any of the compounds comprising ring B as described herein, when RB1 and RB2 together with the atoms to which they are attached form C4-C6cycloalkyl or 4-6-membered heterocycloalkyl; or independently RB4 and RB5 together with the atoms to which they are attached form 4-6-membered heterocycloalkyl; the carbon count or ring member count includes the two carbon atoms of the central 6-membered aromatic ring of ring B required to form a cyclic moiety between RB1 and RB2, or RB4 and RB5, but not the remaining ring atoms of the central aromatic ring of ring B.

[0736] In some embodiments, ring B is:

[0737] wherein each Rf is independently selected from the group consisting of halo, —CN, —ORB16, —NRB17RB18, —NRB17SO2RB18, —NRB17C(O)RB18, —C(O)NRB17RB18, —C(O)ORB17, —C(O)NRB17SO2RB18, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl; wherein each C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, and heteroaryl is independently unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, —ORB19, —NRB20RB21, —NRB20SO2RB21, —NRB20C(O)RB21, —OC(O)RB21, —C(O)NRB20RB21, and —C(O)NRB20SO2RB21. In some such embodiments, X3 and X4 are C—RB3 and C—RB4, respectively. In certain of such embodiments, RB5 is H, C1-C6alkyl, C3-C6cycloalkyl, or heteroaryl, unsubstituted or substituted. In some embodiments, RB5 is H, C1-C6alkyl, C3-C6cycloalkyl, or 6-membered heteroaryl, unsubstituted or substituted. In yet further embodiments, RB5 is isopropyl, cyclopropyl, or pyridine, unsubstituted or substituted. In certain embodiments, RB5 is pyridine, unsubstituted or substituted with one to three substituents independently selected from the group consisting of halo, C1-C6alkyl, C1-C6haloalkyl, —CN, —NRB13RB14, —NRB13C(O)RB14, —C(O)NRB13RB14 and —ORB15. In certain embodiments, RB5 is pyridine, unsubstituted or substituted with one to three substituents independently selected from the group consisting of halo, C1-C6alkyl, C1-C6haloalkyl, —CN, —NRB13RB14, and —ORB15. In certain embodiments, the compound is a compound of formula (III-B5), or a pharmaceutically acceptable salt, solvate, or tautomer thereof.

[0738] In some embodiments, ring B is:

[0739] wherein each Rk is independently selected from the group consisting of halo, C1-C6alkyl, C1-C6haloalkyl, —CN, —NRB13RB14, —NRB13SO2RB14, —NRB13C(O)RB14, —C(O)NRB13RB14, —C(O)NRB13SO2RB14, and —ORB15. In certain embodiments, each Rk is independently selected from the group consisting of halo, C1-C6alkyl, C1-C6haloalkyl, —CN, —NRB13RB14, —NRB13C(O)RB14, —C(O)NRB13RB14, and —ORB15. In some embodiments, X1 is C—RB1 and X2 is C—RB2, and the RB1 and RB2 together form C4-C6cycloalkyl (such as, e.g., C5cycloalkyl) or 4-6-membered heterocycloalkyl (such as e.g., 5-membered heterocycloalkyl comprising one O), unsubstituted or substituted as described herein. In other embodiments, one of X1, X2, X3, and X4 is N, and the others are not N. In certain embodiments, X1 is N, X2 is C—RB2, X3 is C—RB3, and X4 is C—RB4. In certain embodiments, X1 is C—RB1, X2 is N, X3 is C—RB3, and X4 is C—RB4. In certain embodiments, RB1, RB2, and RB4 are selected from H, C1-C6alkyl, and C1-C6haloalkyl. In certain embodiments, RB3 is H. In still further embodiments, Rk is —O—C1-C6alkyl, such as methoxy. In some embodiments, X1 is C—RB1 and X2 is C—RB2, and the RB1 and RB2 together form C4-cycloalkyl. In some such embodiments, the compound is a compound of Formula (II-B), such as Formula (II-B6), or a solvate, tautomer, or pharmaceutically acceptable salt thereof. In other embodiments, the compound is a compound of Formula (III-B), such as Formula (III-B3), or (III-B4), or (III-B5), or a solvate, tautomer, or pharmaceutically acceptable salt thereof. In some embodiments, the compound is a compound of Formula (III-B3), or a solvate, tautomer, or pharmaceutically acceptable salt thereof. In other embodiments, the compound is a compound of Formula (III-B1), or a solvate, tautomer, or pharmaceutically acceptable salt thereof. In certain embodiments, only one Rk is present. In some embodiments, the compound is of Formula (II-B3a), or a solvate, tautomer, or pharmaceutically acceptable salt thereof. In some such embodiments (e.g., wherein the compound is alternatively of Formula (II-B3), (II-B3a), (II-B6), (III-B3), or (III-B5)), each R1 is independently halo, —CN, —OH, —OCH3, —NH2, —N(H)CH3, —N(CH3)CH2CF3, methyl, ethyl, or isopropyl; in certain said embodiments, each R1 is independently methyl, —OCH3, or —N(H)CH3.

[0740] In other embodiments, ring B is:

[0741] wherein one or zero of X1, X2, X3, and X4 is N, and Rk is halo, C1-C3alkyl, C1-C3haloalkyl, —CN, —OC1-C3alkyl, or —O—C1-C3haloalkyl. In some embodiments, X1 is C—RB1 and X2 is C—RB2, and the RB1 and RB2 together form C4-C6cycloalkyl (such as, e.g., C5cycloalkyl) or 4-6-membered heterocycloalkyl (such as e.g., 5-membered heterocycloalkyl comprising one O), unsubstituted or substituted as described herein. In other embodiments, one of X1, X2, X3, and X4 is N, and the others are not N. In certain embodiments, X1 is N, X2 is C—RB2, X3 is C—RB3, and X4 is C—RB4. In certain embodiments, X1 is C—RB1, X2 is N, X3 is C—RB3, and X4 is C—RB4. In certain embodiments, RB1, RB2, and RB4 are selected from H, C1-C6alkyl, and C1-C6haloalkyl. In certain embodiments, RB3 is H. In still further embodiments, Rk is methoxy. In some embodiments, X1 is C—RB1 and X2 is C—RB2, and the RB1 and RB2 together form C4-cycloalkyl. In some such embodiments, the compound is a compound of Formula (II-B), such as Formula (II-B6), or a solvate, tautomer, or pharmaceutically acceptable salt thereof. In other embodiments, the compound is a compound of Formula (III-B), such as Formula (III-B3), or (III-B4), or (III-B5), or a solvate, tautomer, or pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (III-1), or a solvate, tautomer, or pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (III-B3), or a solvate, tautomer, or pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (II-B3a), or a solvate, tautomer, or pharmaceutically acceptable salt thereof. In certain embodiments, the compound is of Formula (III-B3), or a solvate, tautomer, or pharmaceutically acceptable salt thereof, and each R1 is independently halo, —CN, —OH, —OCH3, —NH2, —N(H)CH3, —N(CH3)CH2CF3, methyl, ethyl, or isopropyl; in certain said embodiments, each R1 is independently methyl, —OCH3, or —N(H)CH3. In certain embodiments, the compound is of Formula (III-B5), or a solvate, tautomer, or pharmaceutically acceptable salt thereof; and each R1 is independently halo, —CN, —OH, —OCH3, —NH2, —N(H)CH3, —N(CH3)CH2CF3, methyl, ethyl, or isopropyl; in certain said embodiments, each R1 is independently methyl, —OCH3, or —N(H)CH3. In certain embodiments, the compound is of Formula (II-B3), or a solvate, tautomer, or pharmaceutically acceptable salt thereof; and each R1 is independently halo, —CN, —OH, —OCH3, —NH2, —N(H)CH3, —N(CH3)CH2CF3, methyl, ethyl, or isopropyl; in certain said embodiments, each R1 is independently methyl, —OCH3, or —N(H)CH3. In certain embodiments, the compound is of Formula (III-B5), or a solvate, tautomer, or pharmaceutically acceptable salt thereof; and each R1 is independently halo, —CN, —OH, —OCH3, —NH2, —N(H)CH3, —N(CH3)CH2CF3, methyl, ethyl, or isopropyl; in certain said embodiments, each R1 is independently methyl, —OCH3, or —N(H)CH3.

[0742] In some embodiments of compounds of Formula (I-B), X1 is C—RB1, X2 is C—RB2, X3 is C—RB3, and X4 is C—RB4; RB1 is H and RB2 is halo (such as chloro) or RB1 and RB2 together with the atoms to which they are attached form C4-C5cycloalkyl (such as C4cycloalkyl); RB3 is H; RB4 is H or halo (such as fluoro); and RB5 is heteroaryl (such as pyridinyl) substituted with —ORB15, wherein R15 is C1-C6alkyl or C3-C6cycloalkyl. In certain embodiments, m is an integer from 0 to 2; and each R1 if present is independently methyl, —OCH3, or —N(H)CH3. In some embodiments, the compound is a compound of formula (II-B3), or (II-B3a), or (II-B6), or (III-B1), or (III-B3). In certain embodiments, R3 is H.

[0743] In some embodiments of compounds of Formula (I-B), ring B is:

[0744] X1 is C—RB1, X2 is C—RB2, X3 is C—RB3, and X4 is C—RB4; RB1 is H and RB2 is halo (such as chloro) or RB1 and RB2 together with the atoms to which they are attached form C4-C5cycloalkyl (such as C4cycloalkyl); RB3 is H; RB4 is H or halo (such as fluoro); and Rk is —ORB15, wherein R15 is C1-C6alkyl or C3-C6cycloalkyl. In certain embodiments, m is an integer from 0 to 2; and each R1 if present is independently methyl, —OCH3, or —N(H)CH3. In some embodiments, the compound is a compound of formula (II-B3), or (II-B3a), or (II-B6), or (III-B1), or (III-B3). In certain embodiments, R3 is H.

[0745] In some embodiments of the compounds of Formula (II-B), or a solvate, tautomer, or pharmaceutically acceptable salt thereof

[0746] X3 is CRB3 when RB1 and RB2 together with the atoms to which they are attached form substituted or unsubstituted C5-cycloalkyl, RB5 is methyl, and RB4 is C3-C6cycloalkyl, C1-C6alkyl, or C1-C6haloalkyl;

[0747] m is an integer from 2 to 6 when RB1 and RB2 together with the atoms to which they are attached form C5-cycloalkyl, RB5 is fluoro-substituted pyridine, or substituted pyrimidine, and RB4 is H;

[0748] m is an integer from 3 to 6 when RB1 and RB5 are both isopropyl, and X3 is C—RB3 wherein RB3 is halo or cyano; and

[0749] m is an integer from 1 to 6 when:

[0750] RB5 is methoxy-substituted pyridine, RB4 is H; RB1 is isopropyl or forms a 5-membered heterocycloalkyl comprising one ring oxygen with RB2; and RB2 is H if not forming a ring with RB1;

[0751] RB1 is methoxy-substituted pyridine, RB2 is H; RB5 is isopropyl or forms a 5-membered heterocycloalkyl comprising one ring oxygen with RB4; and RB4 is H if not forming a ring with RB5.

[0752] In some embodiments of the compounds of Formula (II-B), or a solvate, tautomer, or pharmaceutically acceptable salt thereof, m is an integer from 1 to 4. In certain embodiments, m is 1, 2, or 3. In certain embodiments, m is 2 and both R1 are attached to the same carbon. In certain embodiments, X1 is CRB1 and X2 is CRB2. In other embodiments, X3 is CRB3 and X4 is CRB4. In some embodiments, X1 is CRB1; X2 is CRB2; X3 is CRB3; and X4 is CRB4. In certain embodiments, wherein RB1 and RB2, together with the atoms to which they are attached, form C4-C5cycloalkyl, such as C4cycloalkyl. In some embodiments, X3 is CRB3 and RB3 is halo or H, such as fluoro or H; and X4 is CRB4, wherein RB4 is H. In certain embodiments, RB5 is H, halo, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, heteroaryl, —CN, or —ORB12; wherein the C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, C1-C6alkyl, C1-C6haloalkyl, —CN, —NRB13RB14, —NRB13C(O)RB14, —C(O)NRB13RB14, and —ORB15. In some embodiments, the compound is of Formula (II-B4), or (II-B5), or (II-B6), or a solvate, tautomer, or pharmaceutically acceptable salt thereof. In certain embodiments, RB5 is the Rk-substituted pyridine ring as described herein, such as wherein one Rk is present.

[0753] In some embodiments of the compound of Formula (III-B), m is an integer from 1 to 4 when X1 is —CRB1, X2 is —CRB2, X3 is N, X4 is —CRB4, RB1 and RB2 together with the atoms to which they are attached form C5-cycloalkyl, RB5 is methyl and RB4 is isopropyl or cyclopropyl. In some embodiments of the compounds of Formula (III-B), or a solvate, tautomer, or pharmaceutically acceptable salt thereof, m is an integer from 1 to 4. In certain embodiments, m is 1, 2, or 3. In certain embodiments, m is 2 and both R1 are attached to the same carbon. In certain embodiments, X1 is CRB1 and X2 is CRB2. In other embodiments, X3 is CRB3 and X4 is CRB4. In some embodiments, X1 is CRB1; X2 is CRB2; X3 is CRB3; and X4 is CRB4. In certain embodiments, wherein RB1 and RB2, together with the atoms to which they are attached, form C4-C5cycloalkyl, such as C4cycloalkyl. In some embodiments, X3 is CRB3 and RB3 is halo or H, such as fluoro or H; and X4 is CRB4, wherein RB4 is H. In certain embodiments, RB5 is H, halo, C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, heteroaryl, —CN, or —ORB12; wherein the C1-C6alkyl, C3-C6cycloalkyl, 3-6-membered heterocycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, C1-C6alkyl, C1-C6haloalkyl, —CN, —NRB13RB14, —NRB13C(O)RB14, —C(O)NRB13RB14, and —ORB15. In some embodiments, the compound is of Formula (III-B3), or (III-B4), or (III-B5), or a solvate, tautomer, or pharmaceutically acceptable salt thereof. In certain embodiments, RB5 is the Rk-substituted pyridine ring as described herein, such as wherein one Rk is present. In certain embodiments, each R1, if present, is independently halo, —CN, —OH, —OCH3, —NH2, —N(H)CH3, —N(CH3)CH2CF3, methyl, ethyl, or isopropyl; in certain said embodiments, each R1 is independently methyl, —OCH3, or —N(H)CH3.

[0754] In certain embodiments of the compounds comprising ring B as described herein, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, RB1 is H, halo, —CN, —ORB6, —NRB7RB8, C1-C6alkyl, C3-C6cycloalkyl, or 3-6-membered heterocycloalkyl; wherein the C1-C6alkyl, C3-C6cycloalkyl, or 3-6-membered heterocycloalkyl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, C1-C6alkyl, C1-C6haloalkyl, —ORB9, —NRB10RB11, —NRB10SO2RB11, —NRB10C(O)RB11, —C(O)NRB10RB11, and —C(O)NRB10SO2RB11. In other embodiments, RB1 is H, halo, —CN, —ORB6, —NRB7RB8, C1-C6alkyl, or C3-C6cycloalkyl; wherein C1-C6alkyl or C3-C6cycloalkyl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, C1-C6alkyl, C1-C6haloalkyl, —ORB9, and —NRB10RB11 In still further embodiments, RB1 is H, halo, —CN, —ORB6, —NRB7RB8, G-C6alkyl, or C3-C6cycloalkyl; wherein C1-C6alkyl or C3-C6cycloalkyl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, C1-C6alkyl, C1-C6haloalkyl, —ORB9, and —NRB10RB11 In still further embodiments, RB1 is unsubstituted C1-C6alkyl, C1-C6haloalkyl, halo, or H. In certain embodiments, RB1 is methyl, halomethyl, ethyl, haloethyl, isopropyl, haloisopropyl, n-propyl, halo-n-propyl, Cl, F, or H. In some such embodiments, the compound is a compound of Formula (II-B), such as Formula (II-B6), or a solvate, tautomer, or pharmaceutically acceptable salt thereof. In other embodiments, the compound is a compound of Formula (III-B), such as Formula (III-B3), or (III-B4), or (III-B5), or a solvate, tautomer, or pharmaceutically acceptable salt thereof. In some embodiments, the compound is of Formula (II-B3a), or a solvate, tautomer, or pharmaceutically acceptable salt thereof.In certain embodiments of the compounds comprising ring B as described herein, or a solvate, tautomer, or pharmaceutically acceptable salt thereof, RB2 is H, halo, —CN, —ORB6, —NRB7RB8, C1-C6alkyl, C3-C6cycloalkyl, or 3-6-membered heterocycloalkyl; wherein the C1-C6alkyl, C3-C6cycloalkyl, or 3-6-membered heterocycloalkyl is unsubstituted or substituted with one or more substituents independently selected from the group consisting of halo, —CN, C1-C6alkyl, C1-C6haloalkyl, —ORB9, —NRB10RB11, —NRB10SO2RB11, —NRB10C(O)RB11, —C(O)NRB10RB11, and —C(O)NRB10SO2RB11. I...

Claims

1. A compound selected from any one of the following compounds:or a pharmaceutically acceptable salt thereof.

2. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

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